DPP4 Gene Polymorphism Associates With Type 2 Diabetes Mellitus in Older Adults (original) (raw)
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Diabetes Research and Clinical Practice, 2016
We aimed to determine serum dipeptidyl peptidase-4 (DPP-4) activity in a group of persons with latent autoimmune diabetes in adults (LADA) and to compare it with persons with type 1, type 2 diabetes and healthy controls. Methods: DPP-4 activity measurement was performed in 67 persons (21 with type 1, 26 type 2 and 19 with LADA) and 13 healthy age and gender matched controls. Results: Persons with LADA showed highest DPP-4 activity among the study groups (32.71±3.55 vs 25.37±2.84 vs 18.57±2.54 vs 18.57±2.61 U/L p<0.001). Mean glutamic acid autoantibody in persons with LADA was 164.32±86.28 IU/mL. It correlated with DPP-4 activity (r=0.484, p=0.013). Furthermore, DPP-4 activity correlated with waist circumference (r=0.279, p=0.034) and glycated haemoglobin A1c (r=0.483, p<0.001), as well as with LDL cholesterol (r=0.854, p<0.001) and total daily insulin dose (r=0.397, p=0.001). In the multinomial regression analysis DPP-4 activity remained associated with both LADA (prevalence ratio 1.058 (1.012-1.287), p=0.001) and type 1 diabetes (prevalence ratio 1.506 (1.335-1.765), p<0.001) while it did not show an association with type 2 diabetes (prevalence ratio 0.942 (0.713-1.988), p=0.564). Conclusions: Persons with LADA express higher DPP-4 activity compared to persons with both type 1 and type 2 diabetes. The possible patophysiological role of DPP-4 in the LADA pathogenesis needs to be further evaluated.
Frontiers in Genetics, 2021
Dipeptidyl peptidase-4 (DPP4) can influence lipid homeostasis and atherosclerosis progression. We aimed to assess the association of DPP4 gene polymorphisms with hypoalphalipoproteinemia and DPP4 serum levels, in a cohort of Mexican individuals. Five DPP4 polymorphisms (rs12617336, rs12617656, rs1558957, and rs3788979, and rs17574) were genotyped in 748 participants with and 745 without hypoalphalipoproteinemia. The associations were evaluated using logistic regression analyses. Under inheritance models adjusted for confounding variables, the rs12617336 (OR = 0.22, Pheterozygote = 0.001) and rs17574 (OR = 0.78, Padditive = 0.022; OR = 0.73, Pdominant = 0.012; OR = 0.73, Pheterozygote = 0.017; OR = 0.72, Pcodominant1 = 0.014) minor alleles were associated with a low risk of hypoalphalipoproteinemia. After the correction for multiple comparisons, the associations were marginal except the association of the rs12617336 that remaining significant. Additionally, both DPP4 minor alleles we...
Pharmacogenetics of dipeptidyl peptidase 4 inhibitors in a Taiwanese population with type 2 diabetes
Oncotarget
Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral anti-hyperglycemic drugs enabling effective glycemic control in type 2 diabetes (T2D). Despite DPP-4 inhibitors' advantages, the patients' therapeutic response varies. In this retrospective cohort study, 171 Taiwanese patients with T2D were classified as sensitive or resistant to treatment based on the mean change in HbA1c levels. Using an assumption-free genome-wide association study, 45 single nucleotide polymorphisms (SNPs) involved in the therapeutic response to DPP-4 inhibitors (P < 1 × 10-4) were identified at or near PRKD1, CNTN3, ASK, and LOC10537792. A SNP located within the fourth intron of PRKD1 (rs57803087) was strongly associated with DPP-4 inhibitor response (P = 3.2 × 10-6). This is the first pharmacogenomics study on DPP-4 inhibitor treatment for diabetes in a Taiwanese population. Our data suggest that genes associated with β-cell function and apoptosis are involved in the therapeutic effect of DPP-4 inhibitors, even in the presence of additional oral anti-diabetic drugs. Our findings provide information on how genetic variants influence drug response and may benefit the development of personalized medicine.
Enzyme activity and genetic polymorphisms in patients with type II diabetes mellitus
Advances in Clinical and Experimental Medicine, 2020
Background. Diabetes mellitus (DM) has become more and more common and has a high morbidity and mortality rate worldwide. It is a multifactorial chronic disease affected by both genetic and environmental factors. Objectives. To evaluate the association between antioxidant enzyme activities and their genetic variations and the level of malondialdehyde (MDA) in type II diabetes patients living in the Adıyaman province in the southeast part of Turkey. Material and methods. One hundred patients diagnosed with type II DM (T2DM) and 100 healthy controls were included in the study. Malondialdehyde levels and antioxidant enzyme activities were measured spectrophometrically. DNA isolation was performed and genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. Our results revealed no significant differences in genotype distributions and allele frequencies of all polymorphisms between groups (p > 0.05). Significantly elevated MDA levels and a significant reduction in catalase (CAT) and paraoxonase (PON) enzyme activities were observed in patients compared to the control group in terms of study groups and genetic variations (p < 0.05). Moreover, CAT activity was reduced in TT genotype in terms of CAT-262 C/T polymorphism in patients (p < 0.05). Paraoxonase activity was observed to be lower in MM genotype in both groups (p < 0.05). Conclusions. CAT-262 C/T polymorphism may be one of the factors that lead to severe clinical situation in DM. Our results suggest that TT genotype may be more prone to lipid peroxidation.
2020
Background: Dipeptidyl peptidase-4 (DPP4) can influence lipid homeostasis and atherosclerosis progression. Our aim was to assess the association of DPP4 gene polymorphisms with hypoalphalipoproteinemia and DPP4 levels, in a cohort of Mexican individuals.Methods: Five DPP4 polymorphisms (rs12617336, rs12617656, rs1558957, rs3788979, rs17574) were genotyped in 748 participants with and 745 without hypoalphalipoproteinemia. The associations were evaluated using logistic regression analyses.Results: Under inheritance models adjusted for confounding variables, the rs12617336 (OR = 0.22, Pheterozygote = 0.001) and rs17574 (OR = 0.79, Padditive = 0.033; OR = 0.75, Pdominant = 0.021; OR = 0.75, Pheterozygote = 0.029; OR = 0.74, Pcodominant1 = 0.024) polymorphisms were associated with a low risk of hypoalphalipoproteinemia. Moreover, GTTCG haplotype was also related with a low risk of this condition (OR = 0.75, P = 0.021). Additionally, both polymorphisms were associated with protection for ...
Nutrition & diabetes, 2018
Several polymorphisms have been associated with obesity and type 2 diabetes in different populations. To investigate the frequencies of a genetic polymorphism of vitamin D receptor (FokI and BsmI) in patients with T2D. The case-control study was conducted in 138 patients with T2D and 172 control subjects, men and women (60-79 years old). The genotype and allele frequency determination of VDR polymorphisms were determined in these subjects. The frequency of the C allele of the FokI polymorphism was significantly higher in the T2D group than in healthy subjects (p = 0.025). The frequencies of the BsmI variant were similar in subjects with and without T2D (p = 0.747). Consistent with these data, there was an association of the C allele with T2D (OR = 1.74, 95% CI = 1.003-3.084, p = 0.036), but not the AG + GG variants for BsmI (OR = 1.02, 95% CI = 0.635-1.649, p = 0.916). We can observe a significant association between carrier of the T > C variant of FokI and type 2 diabetes, adjus...
Genotype and phenotype correlations in diabetic patients in Uruguay
Genetics and Molecular Research, 2009
Genotype and phenotype correlations in diabetic patients cording to the presence or absence of the genetic markers. We found that a higher percentage of people than expected have immunological disease, independent of their phenotype, with a relative risk of 4.62 (95% confidence interval). This methodology allowed us to establish an association between the genotype and its resulting phenotype. We found significant differences; the phenotypic classification did not reflect immunological disease based on genotype. Moreover, when we examined markers, body mass index and age of onset, we found that many people have an intermediate phenotype between type 1 and type 2. This genetic data can help provide an accurate definition of the disease and would therefore provide the physician a better possibility of providing adequate treatment.
Clinical Biochemistry, 2015
Objectives: Dipeptidyl peptidase-4 (DPP4) was recently proposed as a novel adipokine linked to insulin resistance (IR). As IR represents a cluster of disorders in hepatic and muscle cell insulin signalisation, we aimed to assess the possible correlation between fasting serum DPP4 activity, IR and liver enzymes in order to elucidate the question of hepatic contribution to serum DPP4 activity. Design and methods: This cross-sectional study comprised 44 T1DM patients aged 18 to 65 years. IR was estimated using the equation derived from euglycemic-hyperinsulinemic clamp studies-estimated glucose disposal rate (eGDR). DPP4 serum activity was determined spectrophotometrically as a rate of cleavage of 7-amino-4-methyl coumarin (AMC) from H-Gly-Pro-AMC. The patients were divided into two groups according to the mean value of fasting serum DPP4 activity (31.42 U/L). Results: The group with lower fasting serum DPP4 activity had lower mean rate of liver biomarkers alanine aminotransferase (ALT) (p = 0.001) and aspartate aminotransferase (AST) (p = 0.002) while higher eGDR (p = 0.003) compared to group with higher DPP4 activity. DPP4 activity showed positive correlation with AST (r = 0.358, p = 0.017) and ALT (r = 0.364, p = 0.015) while negative correlation with eGDR (r = −0.612, p b 0.001). ALT remained positively associated with fasting serum DPP4 activity after controlling for age, gender, diabetes duration, the use of statins and antihypertensives (p = 0.025). Conclusions: Fasting serum DPP4 activity might be associated with hepatic IR in T1DM patients and a part of soluble DPP4 activity might be of a hepatic origin. Further study investigation is warranted to elucidate this topic.