B. Bailo | University of Toronto (original) (raw)

Papers by B. Bailo

Research paper thumbnail of Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress

Biologics : targets & therapy, 2011

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and certain population ... more The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and certain population subgroups are especially vulnerable to the disease. To reduce T2DM risk and progression at the population level, preventative strategies are needed that can be implemented on a population-wide scale with minimal cost and effort. Chronic low-grade inflammation resulting from oxidative stress and imbalances in the innate immune system has been associated with obesity, metabolic syndrome, and insulin resistance - critical stages in the development and progression of T2DM. Therefore, inflammation may play a causal role in the pathogenesis of T2DM, and reducing it via modulation of oxidative stress and the innate immune response could lead to a status of improved insulin sensitivity and delayed disease onset. Dietary supplementation with anti-inflammatory and antioxidant nutritional factors, such as micronutrients, might present a novel strategy toward the prevention and control of T2DM at th...

Research paper thumbnail of Plasma vitamin D, hormonal contraceptive use, and biomarkers of cardiometabolic disease

Research paper thumbnail of A genome-wide association study (GWAS) of the human plasma proteome

Research paper thumbnail of Identifying markers of insulin resistance in the plasma proteome

Research paper thumbnail of Peer Reviewed: Plasma Vitamin D and Biomarkers of Cardiometabolic Disease Risk in Adult Canadians, 2007–2009

Research paper thumbnail of The Utility of Vitamins in the Prevention of Type 2 Diabetes Mellitus and Its Complications: A Public Health Perspective

Diabetes Mellitus - Insights and Perspectives, 2013

Research paper thumbnail of ABO Genotype, ‘Blood-Type’ Diet and Cardiometabolic Risk Factors

PLoS ONE, 2014

The 'Bloo... more The 'Blood-Type' diet advises individuals to eat according to their ABO blood group to improve their health and decrease risk of chronic diseases such as cardiovascular disease. However, the association between blood type-based dietary patterns and health outcomes has not been examined. The objective of this study was to determine the association between 'blood-type' diets and biomarkers of cardiometabolic health and whether an individual's ABO genotype modifies any associations. Subjects (n = 1,455) were participants of the Toronto Nutrigenomics and Health study. Dietary intake was assessed using a one-month, 196-item food frequency questionnaire and a diet score was calculated to determine relative adherence to each of the four 'Blood-Type' diets. ABO blood group was determined by genotyping rs8176719 and rs8176746 in the ABO gene. ANCOVA, with age, sex, ethnicity, and energy intake as covariates, was used to compare cardiometabolic biomarkers across tertiles of each 'Blood-Type' diet score. Adherence to the Type-A diet was associated with lower BMI, waist circumference, blood pressure, serum cholesterol, triglycerides, insulin, HOMA-IR and HOMA-Beta (P<0.05). Adherence to the Type-AB diet was also associated with lower levels of these biomarkers (P<0.05), except for BMI and waist circumference. Adherence to the Type-O diet was associated with lower triglycerides (P<0.0001). Matching the 'Blood-Type' diets with the corresponding blood group did not change the effect size of any of these associations. No significant association was found for the Type-B diet. Adherence to certain 'Blood-Type' diets is associated with favorable effects on some cardiometabolic risk factors, but these associations were independent of an individual's ABO genotype, so the findings do not support the 'Blood-Type' diet hypothesis.

Research paper thumbnail of Novel Effects of Hormonal Contraceptive Use on the Plasma Proteome

PLoS ONE, 2012

Background: Hormonal contraceptive (HC) use may increase cardiometabolic risk; however, the effec... more Background: Hormonal contraceptive (HC) use may increase cardiometabolic risk; however, the effect of HC on emerging cardiometabolic and other disease risk factors is not clear.

Research paper thumbnail of Genetic Variation in Taste and Its Influence on Food Selection

OMICS: A Journal of Integrative Biology, 2009

Taste perception plays a key role in determining individual food preferences and dietary habits. ... more Taste perception plays a key role in determining individual food preferences and dietary habits. Individual differences in bitter, sweet, umami, sour, or salty taste perception may influence dietary habits, affecting nutritional status and nutrition-related chronic disease risk. In addition to these traditional taste modalities there is growing evidence that "fat taste" may represent a sixth modality. Several taste receptors have been identified within taste cell membranes on the surface of the tongue, and they include the T2R family of bitter taste receptors, the T1R receptors associated with sweet and umami taste perception, the ion channels PKD1L3 and PKD2L1 linked to sour taste, and the integral membrane protein CD36, which is a putative "fat taste" receptor. Additionally, epithelial sodium channels and a vanilloid receptor, TRPV1, may account for salty taste perception. Common polymorphisms in genes involved in taste perception may account for some of the interindividual differences in food preferences and dietary habits within and between populations. This variability could affect food choices and dietary habits, which may influence nutritional and health status and the risk of chronic disease. This review will summarize the present state of knowledge of the genetic variation in taste, and how such variation might influence food intake behaviors.

Research paper thumbnail of Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study

Nutrition & Metabolism, 2012

Background: Inflammation and oxidative stress are associated with the development of numerous chr... more Background: Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Methods: Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson's correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates.

Research paper thumbnail of Positive Association Between 25-Hydroxyvitamin D and C-Reactive Protein is Confounded by Hormonal Contraceptive Use

Journal of Women's Health, 2013

Studies of the relationship between vitamin D and inflammation are equivocal. This may be due to ... more Studies of the relationship between vitamin D and inflammation are equivocal. This may be due to unaccounted confounding. Hormonal contraceptive (HC) use is associated with elevated circulating 25-hydroxyvitamin D [25(OH)D] in Caucasians and African-Americans, but its effects on 25(OH)D in other ethnicities are unclear. HC use is associated with elevated C-reactive protein (CRP), an inflammatory biomarker. Our objectives were to assess the effect of HC use on 25(OH)D across ethnic groups, and to examine the association between HC, 25(OH)D and CRP in an ethnically diverse population of young adults. We recruited Caucasian, East Asian, and South Asian individuals (n=1,403) from Toronto, Canada. Fasting blood measures of 25(OH)D and CRP were obtained. Across ethnic groups, women HC users (n=280) had higher 25(OH)D and CRP than women HC non-users (n=695) and men (n=428) (p<0.008 and p<0.0001, respectively). Circulating 25(OH)D was positively associated with CRP in the entire population in models not accounting for HC use (β=0.010±0.003; p<0.0001). There was no association when men and women HC non-users were examined separately. Among women HC users, there was no association after accounting for hormone dose. A positive association between 25(OH)D and CRP among individuals above the median 25(OH)D (≥51.9 nmol/L) was not significant after adjustment for HC use. No association was observed among individuals below the median. HC use and 25(OH)D were positively associated across ethnic groups. We found no association between 25(OH)D and CRP when HC use was accounted for. HC use confounds the association between 25(OH)D and CRP.

Research paper thumbnail of Glutathione S -Transferase (GST) M1, but Not GSTT1, Genotype Influences Plasma Proteomic Profiles in Caucasian and East Asian Young Adults

Journal of Proteome Research, 2012

Glutathione S-transferase (GST) M1 and T1 are major detoxifying enzymes that have been associated... more Glutathione S-transferase (GST) M1 and T1 are major detoxifying enzymes that have been associated with a number of chronic diseases, but their effect on various physiological pathways remains unclear. We investigated the association between the common GSTM1 and GSTT1 genotypes and multiple disease-related high-abundance proteins of the plasma proteome in young Caucasian (n = 476) and East Asian (n = 352) adults. Overnight fasting blood samples were collected, and 54 high-abundance plasma proteins from several physiological pathways were quantified by mass spectrometry-based multiple reaction monitoring (LC-MRM/MS). Subjects were genotyped for GSTM1 and GSTT1 deletion polymorphisms. Principal component analysis was used to identify proteomic profiles, and differences in individual protein concentrations between genotypes were assessed by ANCOVA. Among Caucasians, 19 proteins differed between GSTM1 genotypes (P < 0.05), with all protein concentrations being higher among the null genotypes. However, only complement C3 reached the Bonferroni-corrected significance threshold for multiple testing (P < 0.0009). Among East Asians, three proteins differed between GSTM1 genotypes (P < 0.05) with higher concentrations among the null genotypes, but none reached the Bonferroni level of significance. Protein concentrations did not differ between GSTT1 genotypes in either ethnicity. These findings suggest that GSTM1 may have novel physiological effects related to immunity and cardiometabolic disease.

Research paper thumbnail of Plasma 25-Hydroxyvitamin D, Hormonal Contraceptive Use, and the Plasma Proteome in Caucasian, East Asian, and South Asian Young Adults

Journal of Proteome Research, 2013

Vitamin D affects gene expression, but its downstream effects on the proteome are unclear. Hormon... more Vitamin D affects gene expression, but its downstream effects on the proteome are unclear. Hormonal contraceptives (HC), which affect vitamin D metabolism and have widespread effects on the plasma proteome, may confound the association between vitamin D and the proteome. We determined whether HC use modified the association between 25-hydroxyvitamin D (25D) and a panel of 54 high-abundance plasma proteins. Cross-sectional analyses were conducted in healthy, nonsmoking female HC users (n = 216), female HC nonusers (n = 502), and men (n = 301) from Toronto, Canada. Plasma 25D was measured by HPLC-MS/MS, and proteins were measured by LC-multiple-reaction-monitoring (MRM)-MS. The 54 proteins clustered into four distinct proteomic profiles. A positive association was observed between Profile 1, containing positive acute phase proteins, and 25D. In female HC users, a J-shaped association existed between Profile 1 and 25D, but no associations existed in female HC nonusers and men. Twelve proteins were individually associated with 25D in female HC users, but only two were associated with 25D in female HC nonusers and no associations were observed in men. After accounting for hormone dose, only three proteins were associated with 25D. In summary, HC use is an important confounder of the association between circulating 25D and numerous plasma proteins.

Research paper thumbnail of Association between the plasma proteome and serum ascorbic acid concentrations in humans

The Journal of Nutritional Biochemistry, 2013

Vitamin C has been associated with a reduced risk of chronic diseases, but the biological pathway... more Vitamin C has been associated with a reduced risk of chronic diseases, but the biological pathways regulated by vitamin C are not all known. The objective was to use a proteomics approach to identify plasma proteins associated with circulating levels of ascorbic acid. Men and women (n=1022) 20-29 years of age from the Toronto Nutrigenomics and Health Study completed a general health and lifestyle questionnaire and a 196-item food frequency questionnaire and provided a fasting blood sample. Circulating ascorbic acid was analyzed by high-performance liquid chromatography, and a mass-spectrometry-based multiple reaction monitoring method was used to measure 54 proteins abundant in plasma that are involved in numerous physiologic pathways. Mean protein concentrations were compared across tertiles of serum ascorbic acid using analysis of covariance adjusted for sex, ethnocultural group, season of blood draw, hormonal contraceptive use among women, waist circumference and tertiles of plasma α-tocopherol. A Bonferroni significance level of P<.0009 was applied, and analyses were adjusted for multiple comparisons using the Tukey-Kramer procedure. Levels of complement C9, ceruloplasmin, alpha-1-anti-trypsin, angiotensinogen, complement C3, vitamin D binding protein and plasminogen were inversely associated with levels of ascorbic acid. The inverse association between ascorbic acid and vitamin D binding protein was highest in those with higher levels of serum 25-hydroxyvitamin D. In conclusion, several plasma proteins from various physiologic pathways are significantly associated with circulating levels of ascorbic acid. These findings suggest that vitamin C may have novel physiological effects.

Research paper thumbnail of Association between the plasma proteome and plasma α-tocopherol concentrations in humans

The Journal of Nutritional Biochemistry, 2013

Vitamin E is a lipophilic antioxidant that has been inversely associated with certain chronic dis... more Vitamin E is a lipophilic antioxidant that has been inversely associated with certain chronic diseases; however, the biological processes regulated by this vitamin have not been fully elucidated. The objective of the present study was to examine the association between the most biologically active and abundant form of vitamin E in the circulation, α-tocopherol, and the plasma proteome. Subjects were from the Toronto Nutrigenomics and Health Study and included men and women (n=1,022) who completed a general health and lifestyle questionnaire and 196-item food frequency questionnaire, and provided a fasting blood sample. Plasma α-tocopherol concentrations were measured by high-performance liquid chromatography and 54 plasma proteins were assayed by a mass spectrometry-based multiple reaction monitoring method. Analysis of covariance was used to compare mean concentrations of plasma proteins across tertiles of α-tocopherol. Plasma concentrations of apolipoprotein C-III, fibrinogen alpha, beta, and gamma chains, fibronectin and fibrinopeptide A were significantly and positively associated with plasma α-tocopherol, while intermediate levels of α-tocopherol were significantly associated with higher levels of alpha-1B-glycoprotein (all P<.0009). These findings show that circulating levels of α-tocopherol are significantly associated with specific plasma proteins and suggest novel physiological effects of vitamin E.

Research paper thumbnail of Genetic Variation in the Vitamin D Receptor, Plasma 25-Hydroxyvitamin D, and Biomarkers of Cardiometabolic Disease in Caucasian Young Adults

Journal of Nutrigenetics and Nutrigenomics, 2013

Vitamin D regulates gene transcription by binding to the vitamin D receptor (VDR), potentially af... more Vitamin D regulates gene transcription by binding to the vitamin D receptor (VDR), potentially affecting cardiometabolic disease risk. However, studies of 25-hydroxyvitamin D [25(OH)D] and cardiometabolic disease are inconsistent. Inconsistencies may result from unaccounted for interactions between VDR genetic variants and 25(OH)D. We examined the effect of 25(OH)D on the association between VDR variants and cardiometabolic disease biomarkers. The relationship between 25(OH)D, 24 VDR variants, and 10 cardiometabolic biomarkers was examined in 488 Caucasians aged 20-29 years. Covariate-adjusted general linear models were used to examine the interaction effect of 25(OH)D × VDR on each biomarker. When interactions were significant (p < 0.05), relationships were further examined with analysis of covariance, stratified by tertiles of 25(OH)D and adjusted for multiple comparisons. In the lowest tertile of 25(OH)D, major allele homozygotes for rs3819545 had higher insulin and HOMA-IR than minor allele carriers (p ≤ 0.002). Fasting insulin and HOMA-IR were lower in the highest than the lowest tertile of 25(OH)D among major allele homozygotes (p < 0.0001), but minor allele carriers had similar levels regardless of vitamin D status. We identified 25(OH)D-dependent associations between rs3819545 and glycemic dysregulation biomarkers. Major allele homozygotes with low vitamin D status may be at increased risk of insulin resistance.

Research paper thumbnail of A common polymorphism near the interleukin-6 gene modifies the association between dietary fat intake and insulin sensitivity

Journal of Inflammation Research, 2012

Background: Increasing evidence suggests a role for inflammation in the development of type 2 dia... more Background: Increasing evidence suggests a role for inflammation in the development of type 2 diabetes. Elevated levels of inflammatory cytokines, including interleukin-6, have been associated with insulin resistance, and dietary lipids can increase cytokine production. The objective of this study was to determine whether a single nucleotide polymorphism near the IL6 gene (rs7801406) modifies the relationship between dietary fat and markers of insulin sensitivity. Methods: Subjects were healthy men and women aged 20-29 years from the Toronto Nutrigenomics and Health Study. Dietary intake was estimated using a one-month semiquantitative food frequency questionnaire. Fasting blood samples were taken for genotyping and biomarker measurement. Results: The single nucleotide polymorphism was not associated with any of the measures of insulin sensitivity. However, it modified the relationship between total dietary fat and the homeostasis model assessment of insulin resistance (P = 0.053 for interaction). Total fat intake was positively related to HOMA-IR in individuals homozygous for the G allele (β = 0.005 ± 0.002, P = 0.03), but not among heterozygotes. There was an inverse relationship between total fat intake and HOMA-IR in individuals who were homozygous for the A allele (β = −0.012 ± 0.006, P = 0.047). Conclusion: These findings suggest that dietary fat influences insulin sensitivity differently depending on genotype.

Research paper thumbnail of P2-32 Vitamin D in the prediction of metabolic syndrome: a target for public health intervention

Journal of Epidemiology & Community Health, 2011

Research paper thumbnail of P2-31 Association between plasma vitamin D and metabolic syndrome in the Canadian population

Journal of Epidemiology & Community Health, 2011

Research paper thumbnail of The association between obesity, cardiometabolic disease biomarkers, and innate immunity-related inflammation in Canadian adults

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2012

Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease... more Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese Canadian adults. Methods: Subjects (n = 1805, aged 18 to 79 years) from the Canadian Health Measures Survey (CHMS) were examined for associations between BMI, cardiometabolic markers (apolipoprotein [Apo] A1, ApoB, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, total cholesterol/HDL ratio [total:HDL-C ratio], triglycerides, and glycosylated hemoglobin [HbA 1c ]), inflammatory factors (C-reactive protein [CRP], fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit, for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in Canadian adults. Results: All biomarkers were significantly associated with BMI (P # 0.001). ApoA1 (β = −0.31, P , 0.0001), HDL-C (β = −0.61, P , 0.0001), and 25(OH)D (β = −0.25, P , 0.0001) were inversely associated with BMI, while all other biomarkers showed positive linear associations. Distinct patterns of association were noted among normal weight, overweight, and obese groups, excluding CRP which showed a significant positive association with BMI in the overall population (β = 2.80, P , 0.0001) and in the normal weight (β = 3.20, P = 0.02), overweight (β = 3.53, P = 0.002), and obese (β = 2.22, P = 0.0002) groups. Conclusions: There is an apparent profile of cardiometabolic and inflammatory biomarkers that emerges as BMI increases from normal weight to obesity. Understanding these profiles may permit developing an effective approach for early risk prediction for cardiometabolic disease.

Research paper thumbnail of Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress

Biologics : targets & therapy, 2011

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and certain population ... more The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and certain population subgroups are especially vulnerable to the disease. To reduce T2DM risk and progression at the population level, preventative strategies are needed that can be implemented on a population-wide scale with minimal cost and effort. Chronic low-grade inflammation resulting from oxidative stress and imbalances in the innate immune system has been associated with obesity, metabolic syndrome, and insulin resistance - critical stages in the development and progression of T2DM. Therefore, inflammation may play a causal role in the pathogenesis of T2DM, and reducing it via modulation of oxidative stress and the innate immune response could lead to a status of improved insulin sensitivity and delayed disease onset. Dietary supplementation with anti-inflammatory and antioxidant nutritional factors, such as micronutrients, might present a novel strategy toward the prevention and control of T2DM at th...

Research paper thumbnail of Plasma vitamin D, hormonal contraceptive use, and biomarkers of cardiometabolic disease

Research paper thumbnail of A genome-wide association study (GWAS) of the human plasma proteome

Research paper thumbnail of Identifying markers of insulin resistance in the plasma proteome

Research paper thumbnail of Peer Reviewed: Plasma Vitamin D and Biomarkers of Cardiometabolic Disease Risk in Adult Canadians, 2007–2009

Research paper thumbnail of The Utility of Vitamins in the Prevention of Type 2 Diabetes Mellitus and Its Complications: A Public Health Perspective

Diabetes Mellitus - Insights and Perspectives, 2013

Research paper thumbnail of ABO Genotype, ‘Blood-Type’ Diet and Cardiometabolic Risk Factors

PLoS ONE, 2014

The 'Bloo... more The 'Blood-Type' diet advises individuals to eat according to their ABO blood group to improve their health and decrease risk of chronic diseases such as cardiovascular disease. However, the association between blood type-based dietary patterns and health outcomes has not been examined. The objective of this study was to determine the association between 'blood-type' diets and biomarkers of cardiometabolic health and whether an individual's ABO genotype modifies any associations. Subjects (n = 1,455) were participants of the Toronto Nutrigenomics and Health study. Dietary intake was assessed using a one-month, 196-item food frequency questionnaire and a diet score was calculated to determine relative adherence to each of the four 'Blood-Type' diets. ABO blood group was determined by genotyping rs8176719 and rs8176746 in the ABO gene. ANCOVA, with age, sex, ethnicity, and energy intake as covariates, was used to compare cardiometabolic biomarkers across tertiles of each 'Blood-Type' diet score. Adherence to the Type-A diet was associated with lower BMI, waist circumference, blood pressure, serum cholesterol, triglycerides, insulin, HOMA-IR and HOMA-Beta (P<0.05). Adherence to the Type-AB diet was also associated with lower levels of these biomarkers (P<0.05), except for BMI and waist circumference. Adherence to the Type-O diet was associated with lower triglycerides (P<0.0001). Matching the 'Blood-Type' diets with the corresponding blood group did not change the effect size of any of these associations. No significant association was found for the Type-B diet. Adherence to certain 'Blood-Type' diets is associated with favorable effects on some cardiometabolic risk factors, but these associations were independent of an individual's ABO genotype, so the findings do not support the 'Blood-Type' diet hypothesis.

Research paper thumbnail of Novel Effects of Hormonal Contraceptive Use on the Plasma Proteome

PLoS ONE, 2012

Background: Hormonal contraceptive (HC) use may increase cardiometabolic risk; however, the effec... more Background: Hormonal contraceptive (HC) use may increase cardiometabolic risk; however, the effect of HC on emerging cardiometabolic and other disease risk factors is not clear.

Research paper thumbnail of Genetic Variation in Taste and Its Influence on Food Selection

OMICS: A Journal of Integrative Biology, 2009

Taste perception plays a key role in determining individual food preferences and dietary habits. ... more Taste perception plays a key role in determining individual food preferences and dietary habits. Individual differences in bitter, sweet, umami, sour, or salty taste perception may influence dietary habits, affecting nutritional status and nutrition-related chronic disease risk. In addition to these traditional taste modalities there is growing evidence that "fat taste" may represent a sixth modality. Several taste receptors have been identified within taste cell membranes on the surface of the tongue, and they include the T2R family of bitter taste receptors, the T1R receptors associated with sweet and umami taste perception, the ion channels PKD1L3 and PKD2L1 linked to sour taste, and the integral membrane protein CD36, which is a putative "fat taste" receptor. Additionally, epithelial sodium channels and a vanilloid receptor, TRPV1, may account for salty taste perception. Common polymorphisms in genes involved in taste perception may account for some of the interindividual differences in food preferences and dietary habits within and between populations. This variability could affect food choices and dietary habits, which may influence nutritional and health status and the risk of chronic disease. This review will summarize the present state of knowledge of the genetic variation in taste, and how such variation might influence food intake behaviors.

Research paper thumbnail of Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study

Nutrition & Metabolism, 2012

Background: Inflammation and oxidative stress are associated with the development of numerous chr... more Background: Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Methods: Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson's correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates.

Research paper thumbnail of Positive Association Between 25-Hydroxyvitamin D and C-Reactive Protein is Confounded by Hormonal Contraceptive Use

Journal of Women's Health, 2013

Studies of the relationship between vitamin D and inflammation are equivocal. This may be due to ... more Studies of the relationship between vitamin D and inflammation are equivocal. This may be due to unaccounted confounding. Hormonal contraceptive (HC) use is associated with elevated circulating 25-hydroxyvitamin D [25(OH)D] in Caucasians and African-Americans, but its effects on 25(OH)D in other ethnicities are unclear. HC use is associated with elevated C-reactive protein (CRP), an inflammatory biomarker. Our objectives were to assess the effect of HC use on 25(OH)D across ethnic groups, and to examine the association between HC, 25(OH)D and CRP in an ethnically diverse population of young adults. We recruited Caucasian, East Asian, and South Asian individuals (n=1,403) from Toronto, Canada. Fasting blood measures of 25(OH)D and CRP were obtained. Across ethnic groups, women HC users (n=280) had higher 25(OH)D and CRP than women HC non-users (n=695) and men (n=428) (p<0.008 and p<0.0001, respectively). Circulating 25(OH)D was positively associated with CRP in the entire population in models not accounting for HC use (β=0.010±0.003; p<0.0001). There was no association when men and women HC non-users were examined separately. Among women HC users, there was no association after accounting for hormone dose. A positive association between 25(OH)D and CRP among individuals above the median 25(OH)D (≥51.9 nmol/L) was not significant after adjustment for HC use. No association was observed among individuals below the median. HC use and 25(OH)D were positively associated across ethnic groups. We found no association between 25(OH)D and CRP when HC use was accounted for. HC use confounds the association between 25(OH)D and CRP.

Research paper thumbnail of Glutathione S -Transferase (GST) M1, but Not GSTT1, Genotype Influences Plasma Proteomic Profiles in Caucasian and East Asian Young Adults

Journal of Proteome Research, 2012

Glutathione S-transferase (GST) M1 and T1 are major detoxifying enzymes that have been associated... more Glutathione S-transferase (GST) M1 and T1 are major detoxifying enzymes that have been associated with a number of chronic diseases, but their effect on various physiological pathways remains unclear. We investigated the association between the common GSTM1 and GSTT1 genotypes and multiple disease-related high-abundance proteins of the plasma proteome in young Caucasian (n = 476) and East Asian (n = 352) adults. Overnight fasting blood samples were collected, and 54 high-abundance plasma proteins from several physiological pathways were quantified by mass spectrometry-based multiple reaction monitoring (LC-MRM/MS). Subjects were genotyped for GSTM1 and GSTT1 deletion polymorphisms. Principal component analysis was used to identify proteomic profiles, and differences in individual protein concentrations between genotypes were assessed by ANCOVA. Among Caucasians, 19 proteins differed between GSTM1 genotypes (P < 0.05), with all protein concentrations being higher among the null genotypes. However, only complement C3 reached the Bonferroni-corrected significance threshold for multiple testing (P < 0.0009). Among East Asians, three proteins differed between GSTM1 genotypes (P < 0.05) with higher concentrations among the null genotypes, but none reached the Bonferroni level of significance. Protein concentrations did not differ between GSTT1 genotypes in either ethnicity. These findings suggest that GSTM1 may have novel physiological effects related to immunity and cardiometabolic disease.

Research paper thumbnail of Plasma 25-Hydroxyvitamin D, Hormonal Contraceptive Use, and the Plasma Proteome in Caucasian, East Asian, and South Asian Young Adults

Journal of Proteome Research, 2013

Vitamin D affects gene expression, but its downstream effects on the proteome are unclear. Hormon... more Vitamin D affects gene expression, but its downstream effects on the proteome are unclear. Hormonal contraceptives (HC), which affect vitamin D metabolism and have widespread effects on the plasma proteome, may confound the association between vitamin D and the proteome. We determined whether HC use modified the association between 25-hydroxyvitamin D (25D) and a panel of 54 high-abundance plasma proteins. Cross-sectional analyses were conducted in healthy, nonsmoking female HC users (n = 216), female HC nonusers (n = 502), and men (n = 301) from Toronto, Canada. Plasma 25D was measured by HPLC-MS/MS, and proteins were measured by LC-multiple-reaction-monitoring (MRM)-MS. The 54 proteins clustered into four distinct proteomic profiles. A positive association was observed between Profile 1, containing positive acute phase proteins, and 25D. In female HC users, a J-shaped association existed between Profile 1 and 25D, but no associations existed in female HC nonusers and men. Twelve proteins were individually associated with 25D in female HC users, but only two were associated with 25D in female HC nonusers and no associations were observed in men. After accounting for hormone dose, only three proteins were associated with 25D. In summary, HC use is an important confounder of the association between circulating 25D and numerous plasma proteins.

Research paper thumbnail of Association between the plasma proteome and serum ascorbic acid concentrations in humans

The Journal of Nutritional Biochemistry, 2013

Vitamin C has been associated with a reduced risk of chronic diseases, but the biological pathway... more Vitamin C has been associated with a reduced risk of chronic diseases, but the biological pathways regulated by vitamin C are not all known. The objective was to use a proteomics approach to identify plasma proteins associated with circulating levels of ascorbic acid. Men and women (n=1022) 20-29 years of age from the Toronto Nutrigenomics and Health Study completed a general health and lifestyle questionnaire and a 196-item food frequency questionnaire and provided a fasting blood sample. Circulating ascorbic acid was analyzed by high-performance liquid chromatography, and a mass-spectrometry-based multiple reaction monitoring method was used to measure 54 proteins abundant in plasma that are involved in numerous physiologic pathways. Mean protein concentrations were compared across tertiles of serum ascorbic acid using analysis of covariance adjusted for sex, ethnocultural group, season of blood draw, hormonal contraceptive use among women, waist circumference and tertiles of plasma α-tocopherol. A Bonferroni significance level of P<.0009 was applied, and analyses were adjusted for multiple comparisons using the Tukey-Kramer procedure. Levels of complement C9, ceruloplasmin, alpha-1-anti-trypsin, angiotensinogen, complement C3, vitamin D binding protein and plasminogen were inversely associated with levels of ascorbic acid. The inverse association between ascorbic acid and vitamin D binding protein was highest in those with higher levels of serum 25-hydroxyvitamin D. In conclusion, several plasma proteins from various physiologic pathways are significantly associated with circulating levels of ascorbic acid. These findings suggest that vitamin C may have novel physiological effects.

Research paper thumbnail of Association between the plasma proteome and plasma α-tocopherol concentrations in humans

The Journal of Nutritional Biochemistry, 2013

Vitamin E is a lipophilic antioxidant that has been inversely associated with certain chronic dis... more Vitamin E is a lipophilic antioxidant that has been inversely associated with certain chronic diseases; however, the biological processes regulated by this vitamin have not been fully elucidated. The objective of the present study was to examine the association between the most biologically active and abundant form of vitamin E in the circulation, α-tocopherol, and the plasma proteome. Subjects were from the Toronto Nutrigenomics and Health Study and included men and women (n=1,022) who completed a general health and lifestyle questionnaire and 196-item food frequency questionnaire, and provided a fasting blood sample. Plasma α-tocopherol concentrations were measured by high-performance liquid chromatography and 54 plasma proteins were assayed by a mass spectrometry-based multiple reaction monitoring method. Analysis of covariance was used to compare mean concentrations of plasma proteins across tertiles of α-tocopherol. Plasma concentrations of apolipoprotein C-III, fibrinogen alpha, beta, and gamma chains, fibronectin and fibrinopeptide A were significantly and positively associated with plasma α-tocopherol, while intermediate levels of α-tocopherol were significantly associated with higher levels of alpha-1B-glycoprotein (all P<.0009). These findings show that circulating levels of α-tocopherol are significantly associated with specific plasma proteins and suggest novel physiological effects of vitamin E.

Research paper thumbnail of Genetic Variation in the Vitamin D Receptor, Plasma 25-Hydroxyvitamin D, and Biomarkers of Cardiometabolic Disease in Caucasian Young Adults

Journal of Nutrigenetics and Nutrigenomics, 2013

Vitamin D regulates gene transcription by binding to the vitamin D receptor (VDR), potentially af... more Vitamin D regulates gene transcription by binding to the vitamin D receptor (VDR), potentially affecting cardiometabolic disease risk. However, studies of 25-hydroxyvitamin D [25(OH)D] and cardiometabolic disease are inconsistent. Inconsistencies may result from unaccounted for interactions between VDR genetic variants and 25(OH)D. We examined the effect of 25(OH)D on the association between VDR variants and cardiometabolic disease biomarkers. The relationship between 25(OH)D, 24 VDR variants, and 10 cardiometabolic biomarkers was examined in 488 Caucasians aged 20-29 years. Covariate-adjusted general linear models were used to examine the interaction effect of 25(OH)D × VDR on each biomarker. When interactions were significant (p < 0.05), relationships were further examined with analysis of covariance, stratified by tertiles of 25(OH)D and adjusted for multiple comparisons. In the lowest tertile of 25(OH)D, major allele homozygotes for rs3819545 had higher insulin and HOMA-IR than minor allele carriers (p ≤ 0.002). Fasting insulin and HOMA-IR were lower in the highest than the lowest tertile of 25(OH)D among major allele homozygotes (p < 0.0001), but minor allele carriers had similar levels regardless of vitamin D status. We identified 25(OH)D-dependent associations between rs3819545 and glycemic dysregulation biomarkers. Major allele homozygotes with low vitamin D status may be at increased risk of insulin resistance.

Research paper thumbnail of A common polymorphism near the interleukin-6 gene modifies the association between dietary fat intake and insulin sensitivity

Journal of Inflammation Research, 2012

Background: Increasing evidence suggests a role for inflammation in the development of type 2 dia... more Background: Increasing evidence suggests a role for inflammation in the development of type 2 diabetes. Elevated levels of inflammatory cytokines, including interleukin-6, have been associated with insulin resistance, and dietary lipids can increase cytokine production. The objective of this study was to determine whether a single nucleotide polymorphism near the IL6 gene (rs7801406) modifies the relationship between dietary fat and markers of insulin sensitivity. Methods: Subjects were healthy men and women aged 20-29 years from the Toronto Nutrigenomics and Health Study. Dietary intake was estimated using a one-month semiquantitative food frequency questionnaire. Fasting blood samples were taken for genotyping and biomarker measurement. Results: The single nucleotide polymorphism was not associated with any of the measures of insulin sensitivity. However, it modified the relationship between total dietary fat and the homeostasis model assessment of insulin resistance (P = 0.053 for interaction). Total fat intake was positively related to HOMA-IR in individuals homozygous for the G allele (β = 0.005 ± 0.002, P = 0.03), but not among heterozygotes. There was an inverse relationship between total fat intake and HOMA-IR in individuals who were homozygous for the A allele (β = −0.012 ± 0.006, P = 0.047). Conclusion: These findings suggest that dietary fat influences insulin sensitivity differently depending on genotype.

Research paper thumbnail of P2-32 Vitamin D in the prediction of metabolic syndrome: a target for public health intervention

Journal of Epidemiology & Community Health, 2011

Research paper thumbnail of P2-31 Association between plasma vitamin D and metabolic syndrome in the Canadian population

Journal of Epidemiology & Community Health, 2011

Research paper thumbnail of The association between obesity, cardiometabolic disease biomarkers, and innate immunity-related inflammation in Canadian adults

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2012

Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease... more Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese Canadian adults. Methods: Subjects (n = 1805, aged 18 to 79 years) from the Canadian Health Measures Survey (CHMS) were examined for associations between BMI, cardiometabolic markers (apolipoprotein [Apo] A1, ApoB, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, total cholesterol/HDL ratio [total:HDL-C ratio], triglycerides, and glycosylated hemoglobin [HbA 1c ]), inflammatory factors (C-reactive protein [CRP], fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit, for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in Canadian adults. Results: All biomarkers were significantly associated with BMI (P # 0.001). ApoA1 (β = −0.31, P , 0.0001), HDL-C (β = −0.61, P , 0.0001), and 25(OH)D (β = −0.25, P , 0.0001) were inversely associated with BMI, while all other biomarkers showed positive linear associations. Distinct patterns of association were noted among normal weight, overweight, and obese groups, excluding CRP which showed a significant positive association with BMI in the overall population (β = 2.80, P , 0.0001) and in the normal weight (β = 3.20, P = 0.02), overweight (β = 3.53, P = 0.002), and obese (β = 2.22, P = 0.0002) groups. Conclusions: There is an apparent profile of cardiometabolic and inflammatory biomarkers that emerges as BMI increases from normal weight to obesity. Understanding these profiles may permit developing an effective approach for early risk prediction for cardiometabolic disease.