Alexandre Pereira | Universidade de Coimbra (original) (raw)

Papers by Alexandre Pereira

Research paper thumbnail of NPHS2 R229Q functional variant is associated with microalbuminuria in the general population

Kidney International, 2004

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Research paper thumbnail of The influence of tumor necrosis factor −308 and C-reactive protein G1059C gene variants on serum concentration of C-reactive protein: evidence for an age-dependent association

Clinica Chimica Acta, 2004

C-reactive protein (CRP) synthesis and activity are modulated both by genetic and environmental f... more C-reactive protein (CRP) synthesis and activity are modulated both by genetic and environmental factors. Data about the influence of genetic factors upon CRP concentration are sparse. We evaluated the hypothesis that allele variations in the genes encoding the CRP and TNF-alpha genes could modulate hs-CRP serum concentration in the general population. Six hundred and eighty-four asymptomatic Brazilian individuals, selected between July 1998 and July 2001, 295 men (43.1%) and 389 women (56.9%) were studied. Laboratory assessment included: serum glucose, cholesterol, triglycerides, thyroid-stimulating hormone, uric acid and CRP measured by a high-sensitivity assay (hs-CRP). TNF -308 and CRP G1059C genotypes were obtained through PCR amplification and restriction enzyme digestion. Serum concentrations of hs-CRP were distributed into population quartiles. There was no significant difference of hs-CRP serum concentration regarding CRP gene G1059C polymorphism. However, there was a tendency for higher hs-CRP serum levels in individuals harboring the TNFA2 allele in quartile 4. In addition, ANOVA factorial modeling using log-transformed hs-CRP serum level as the dependent variable disclosed a significant association between hs-CRP and the TNFA2 allele following stratification for age quartiles (p=0.01). Finally, the presence of TNFA2 allele in this age group increased the odds of being in the fourth quartile of hs-CRP concentration (p<0.05, OR=5.1). These findings suggest an association between a functional genetic variant of the TNF-alpha gene and hs-CRP levels at particular age groups.

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Research paper thumbnail of Association between platelet P2Y12 haplotype and risk of cardiovascular events in chronic coronary disease

Thrombosis Research, 2006

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Research paper thumbnail of NKX2.5 mutations in patients with non-syndromic congenital heart disease

International Journal of Cardiology, 2010

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Research paper thumbnail of Three endothelial nitric oxide (NOS3) gene polymorphisms in hypertensive and normotensive individuals: meta-analysis of 53 studies reveals evidence of publication bias

Journal of Hypertension, 2007

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Research paper thumbnail of 2 Adrenoceptor Functional Gene Variants, Obesity, and Blood Pressure Level Interactions in the General Population

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Research paper thumbnail of Angiotensinogen 235T Allele "Dosage" Is Associated With Blood Pressure Phenotypes

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Research paper thumbnail of Clinical Judgment and Treatment Options in Stable Multivessel Coronary Artery Disease

Journal of The American College of Cardiology, 2006

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Research paper thumbnail of Angiotensinogen M235T polymorphism is associated with coronary artery disease severity

Clinica Chimica Acta, 2005

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Research paper thumbnail of Effect of the G-308A polymorphism of the tumor necrosis factor α gene on the risk of ischemic heart disease and ischemic stroke: A meta-analysis

American Heart Journal, 2007

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Research paper thumbnail of HYPERTENSION, OBESITY AND GNB3 GENE VARIANTS

Clinical and Experimental Pharmacology and Physiology, 2006

1The polymorphism C825T of the gene encoding the G-protein b3-subunit (GNB3) was found to be asso... more 1The polymorphism C825T of the gene encoding the G-protein b3-subunit (GNB3) was found to be associated with an increased prevalence of hypertension in a number of studies. The aim of the present study was to investigate the association between this polymorphism and blood pressure phenotypes in an urban, large and ethnically mixed population of Brazil.2Individuals (n = 1 568) were randomly selected from the general population of the Vitória City metropolitan area. The GNB3 C825T polymorphism was genotyped in each individual. Baseline cardiovascular risk factors were collected for all participants. Cardiovascular risk variables and genotypes were compared using anova and the Chi-squared test for univariate comparisons and logistic regression for multiple comparisons.3A statistically significant interaction between the 825T allele and obesity was observed for systolic blood pressure (SBP; P = 0.02). In fact, the C825T genotype was predictive of SBP only in individuals with increased body mass index (P = 0.02). In addition, in a multiple logistic regression model conducted in the obese population and adjusted for age, sex, ethnicity, diabetes, triglycerides and total cholesterol, the presence of the T allele was significantly associated with a 1.5-fold (95% confidence interval 1.04–2.26) increased risk of hypertension. Lack of statistical power does not explain the absence of other positive gene–environment interactions.4The present results suggest that an important gene ¥ environment interaction may take place between bodyweight regulation and the GNB3 gene. This finding provides further evidence for a role of the 825T allele in hypertension susceptibility and may be used for better disease stratification.The polymorphism C825T of the gene encoding the G-protein b3-subunit (GNB3) was found to be associated with an increased prevalence of hypertension in a number of studies. The aim of the present study was to investigate the association between this polymorphism and blood pressure phenotypes in an urban, large and ethnically mixed population of Brazil.Individuals (n = 1 568) were randomly selected from the general population of the Vitória City metropolitan area. The GNB3 C825T polymorphism was genotyped in each individual. Baseline cardiovascular risk factors were collected for all participants. Cardiovascular risk variables and genotypes were compared using anova and the Chi-squared test for univariate comparisons and logistic regression for multiple comparisons.A statistically significant interaction between the 825T allele and obesity was observed for systolic blood pressure (SBP; P = 0.02). In fact, the C825T genotype was predictive of SBP only in individuals with increased body mass index (P = 0.02). In addition, in a multiple logistic regression model conducted in the obese population and adjusted for age, sex, ethnicity, diabetes, triglycerides and total cholesterol, the presence of the T allele was significantly associated with a 1.5-fold (95% confidence interval 1.04–2.26) increased risk of hypertension. Lack of statistical power does not explain the absence of other positive gene–environment interactions.The present results suggest that an important gene ¥ environment interaction may take place between bodyweight regulation and the GNB3 gene. This finding provides further evidence for a role of the 825T allele in hypertension susceptibility and may be used for better disease stratification.

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Research paper thumbnail of Hemochromatosis gene variants in patients with cardiomyopathy

American Journal of Cardiology, 2001

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Research paper thumbnail of Neurofibromatosis-Noonan syndrome: Molecular evidence of the concurrence of both disorders in a patient

American Journal of Medical Genetics Part A, 2005

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial ano... more Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial anomalies, webbed neck, sternal deformity, heart defects, and, in males, cryptorchidism. PTPN11 encodes SHP2, an important component of several signal transduction pathways that acts as a positive regulator of RAS-mitogen activated protein kinase signaling. Neurofibromatosis type 1 (NF1) is another autosomal dominant disorder characterized by hamartomas in multiple organs. The NF1 gene encodes a GAP-related protein, which acts as a negative regulator of the Ras-mediated signal transduction pathway. Clinical overlap between both syndromes, neurofibromatosis–Noonan syndrome (NFNS) is well known. We studied a female patient with typical findings of NFNS and found two mutations: a novel PTPN11 transversion, 1909A → G, resulting in Gln510Arg, and an NF1 transversion, 2531A → G, resulting in Leu844Arg. She inherited the PTPN11 mutation from her father and had a de novo NF1 mutation. This is the first report of molecular concurrence of both disorders in the same patient. © 2005 Wiley-Liss, Inc.

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Research paper thumbnail of Vascular oxidant stress early after balloon injury: evidence for increased NAD(P)H oxidoreductase activity

Free Radical Biology and Medicine, 2000

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Research paper thumbnail of Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene

Journal of Human Genetics, 2007

Costello syndrome is an autosomal dominant disorder comprising growth deficiency, mental retardat... more Costello syndrome is an autosomal dominant disorder comprising growth deficiency, mental retardation, curly hair, coarse facial features, nasal papillomata, low-set ears with large lobes, cardiac anomalies, redundant skin in palms and soles with prominent creases, dark skin, and propensity to certain solid tumors. HRAS mutations have been implicated in approximately 85% of the affected cases. The clinical overlap among Costello, Noonan, and cardiofaciocutaneous syndromes is now better understood given their common molecular background, such that all these syndromes constitute a class of disorders caused by deregulated RAS-MAPK signaling. We report on a novel KRAS gene mutation in a patient presenting the clinical features typical of Costello syndrome and the additional findings seen in Noonan syndrome. This description emphasizes that a subset of patients with Costello syndrome could harbor mutations in other genes involved in the RAS-MAPK signaling.

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Research paper thumbnail of Angiotensinogen and angiotensin converting enzyme gene polymorphisms and the risk of bipolar affective disorder in humans

Neuroscience Letters, 2000

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Research paper thumbnail of Methylenetetrahydrofolate reductase (MTHFR) c677t gene variant modulates the homocysteine folate correlation in a mild folate-deficient population

Clinica Chimica Acta, 2004

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Research paper thumbnail of Metabolic syndrome and coronary artery disease: Is there a gender specific effect

International Journal of Cardiology, 2006

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Research paper thumbnail of Impact of Diabetes on Five-Year Outcomes of Patients With Multivessel Coronary Artery Disease

Annals of Thoracic Surgery, 2007

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Research paper thumbnail of NPHS2 R229Q functional variant is associated with microalbuminuria in the general population

Kidney International, 2004

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Research paper thumbnail of NPHS2 R229Q functional variant is associated with microalbuminuria in the general population

Kidney International, 2004

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Research paper thumbnail of The influence of tumor necrosis factor −308 and C-reactive protein G1059C gene variants on serum concentration of C-reactive protein: evidence for an age-dependent association

Clinica Chimica Acta, 2004

C-reactive protein (CRP) synthesis and activity are modulated both by genetic and environmental f... more C-reactive protein (CRP) synthesis and activity are modulated both by genetic and environmental factors. Data about the influence of genetic factors upon CRP concentration are sparse. We evaluated the hypothesis that allele variations in the genes encoding the CRP and TNF-alpha genes could modulate hs-CRP serum concentration in the general population. Six hundred and eighty-four asymptomatic Brazilian individuals, selected between July 1998 and July 2001, 295 men (43.1%) and 389 women (56.9%) were studied. Laboratory assessment included: serum glucose, cholesterol, triglycerides, thyroid-stimulating hormone, uric acid and CRP measured by a high-sensitivity assay (hs-CRP). TNF -308 and CRP G1059C genotypes were obtained through PCR amplification and restriction enzyme digestion. Serum concentrations of hs-CRP were distributed into population quartiles. There was no significant difference of hs-CRP serum concentration regarding CRP gene G1059C polymorphism. However, there was a tendency for higher hs-CRP serum levels in individuals harboring the TNFA2 allele in quartile 4. In addition, ANOVA factorial modeling using log-transformed hs-CRP serum level as the dependent variable disclosed a significant association between hs-CRP and the TNFA2 allele following stratification for age quartiles (p=0.01). Finally, the presence of TNFA2 allele in this age group increased the odds of being in the fourth quartile of hs-CRP concentration (p<0.05, OR=5.1). These findings suggest an association between a functional genetic variant of the TNF-alpha gene and hs-CRP levels at particular age groups.

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Research paper thumbnail of Association between platelet P2Y12 haplotype and risk of cardiovascular events in chronic coronary disease

Thrombosis Research, 2006

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Research paper thumbnail of NKX2.5 mutations in patients with non-syndromic congenital heart disease

International Journal of Cardiology, 2010

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Research paper thumbnail of Three endothelial nitric oxide (NOS3) gene polymorphisms in hypertensive and normotensive individuals: meta-analysis of 53 studies reveals evidence of publication bias

Journal of Hypertension, 2007

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Research paper thumbnail of 2 Adrenoceptor Functional Gene Variants, Obesity, and Blood Pressure Level Interactions in the General Population

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Angiotensinogen 235T Allele "Dosage" Is Associated With Blood Pressure Phenotypes

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Clinical Judgment and Treatment Options in Stable Multivessel Coronary Artery Disease

Journal of The American College of Cardiology, 2006

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Research paper thumbnail of Angiotensinogen M235T polymorphism is associated with coronary artery disease severity

Clinica Chimica Acta, 2005

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Research paper thumbnail of Effect of the G-308A polymorphism of the tumor necrosis factor α gene on the risk of ischemic heart disease and ischemic stroke: A meta-analysis

American Heart Journal, 2007

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Research paper thumbnail of HYPERTENSION, OBESITY AND GNB3 GENE VARIANTS

Clinical and Experimental Pharmacology and Physiology, 2006

1The polymorphism C825T of the gene encoding the G-protein b3-subunit (GNB3) was found to be asso... more 1The polymorphism C825T of the gene encoding the G-protein b3-subunit (GNB3) was found to be associated with an increased prevalence of hypertension in a number of studies. The aim of the present study was to investigate the association between this polymorphism and blood pressure phenotypes in an urban, large and ethnically mixed population of Brazil.2Individuals (n = 1 568) were randomly selected from the general population of the Vitória City metropolitan area. The GNB3 C825T polymorphism was genotyped in each individual. Baseline cardiovascular risk factors were collected for all participants. Cardiovascular risk variables and genotypes were compared using anova and the Chi-squared test for univariate comparisons and logistic regression for multiple comparisons.3A statistically significant interaction between the 825T allele and obesity was observed for systolic blood pressure (SBP; P = 0.02). In fact, the C825T genotype was predictive of SBP only in individuals with increased body mass index (P = 0.02). In addition, in a multiple logistic regression model conducted in the obese population and adjusted for age, sex, ethnicity, diabetes, triglycerides and total cholesterol, the presence of the T allele was significantly associated with a 1.5-fold (95% confidence interval 1.04–2.26) increased risk of hypertension. Lack of statistical power does not explain the absence of other positive gene–environment interactions.4The present results suggest that an important gene ¥ environment interaction may take place between bodyweight regulation and the GNB3 gene. This finding provides further evidence for a role of the 825T allele in hypertension susceptibility and may be used for better disease stratification.The polymorphism C825T of the gene encoding the G-protein b3-subunit (GNB3) was found to be associated with an increased prevalence of hypertension in a number of studies. The aim of the present study was to investigate the association between this polymorphism and blood pressure phenotypes in an urban, large and ethnically mixed population of Brazil.Individuals (n = 1 568) were randomly selected from the general population of the Vitória City metropolitan area. The GNB3 C825T polymorphism was genotyped in each individual. Baseline cardiovascular risk factors were collected for all participants. Cardiovascular risk variables and genotypes were compared using anova and the Chi-squared test for univariate comparisons and logistic regression for multiple comparisons.A statistically significant interaction between the 825T allele and obesity was observed for systolic blood pressure (SBP; P = 0.02). In fact, the C825T genotype was predictive of SBP only in individuals with increased body mass index (P = 0.02). In addition, in a multiple logistic regression model conducted in the obese population and adjusted for age, sex, ethnicity, diabetes, triglycerides and total cholesterol, the presence of the T allele was significantly associated with a 1.5-fold (95% confidence interval 1.04–2.26) increased risk of hypertension. Lack of statistical power does not explain the absence of other positive gene–environment interactions.The present results suggest that an important gene ¥ environment interaction may take place between bodyweight regulation and the GNB3 gene. This finding provides further evidence for a role of the 825T allele in hypertension susceptibility and may be used for better disease stratification.

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Research paper thumbnail of Hemochromatosis gene variants in patients with cardiomyopathy

American Journal of Cardiology, 2001

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Research paper thumbnail of Neurofibromatosis-Noonan syndrome: Molecular evidence of the concurrence of both disorders in a patient

American Journal of Medical Genetics Part A, 2005

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial ano... more Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial anomalies, webbed neck, sternal deformity, heart defects, and, in males, cryptorchidism. PTPN11 encodes SHP2, an important component of several signal transduction pathways that acts as a positive regulator of RAS-mitogen activated protein kinase signaling. Neurofibromatosis type 1 (NF1) is another autosomal dominant disorder characterized by hamartomas in multiple organs. The NF1 gene encodes a GAP-related protein, which acts as a negative regulator of the Ras-mediated signal transduction pathway. Clinical overlap between both syndromes, neurofibromatosis–Noonan syndrome (NFNS) is well known. We studied a female patient with typical findings of NFNS and found two mutations: a novel PTPN11 transversion, 1909A → G, resulting in Gln510Arg, and an NF1 transversion, 2531A → G, resulting in Leu844Arg. She inherited the PTPN11 mutation from her father and had a de novo NF1 mutation. This is the first report of molecular concurrence of both disorders in the same patient. © 2005 Wiley-Liss, Inc.

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Research paper thumbnail of Vascular oxidant stress early after balloon injury: evidence for increased NAD(P)H oxidoreductase activity

Free Radical Biology and Medicine, 2000

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Research paper thumbnail of Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene

Journal of Human Genetics, 2007

Costello syndrome is an autosomal dominant disorder comprising growth deficiency, mental retardat... more Costello syndrome is an autosomal dominant disorder comprising growth deficiency, mental retardation, curly hair, coarse facial features, nasal papillomata, low-set ears with large lobes, cardiac anomalies, redundant skin in palms and soles with prominent creases, dark skin, and propensity to certain solid tumors. HRAS mutations have been implicated in approximately 85% of the affected cases. The clinical overlap among Costello, Noonan, and cardiofaciocutaneous syndromes is now better understood given their common molecular background, such that all these syndromes constitute a class of disorders caused by deregulated RAS-MAPK signaling. We report on a novel KRAS gene mutation in a patient presenting the clinical features typical of Costello syndrome and the additional findings seen in Noonan syndrome. This description emphasizes that a subset of patients with Costello syndrome could harbor mutations in other genes involved in the RAS-MAPK signaling.

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Research paper thumbnail of Angiotensinogen and angiotensin converting enzyme gene polymorphisms and the risk of bipolar affective disorder in humans

Neuroscience Letters, 2000

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Research paper thumbnail of Methylenetetrahydrofolate reductase (MTHFR) c677t gene variant modulates the homocysteine folate correlation in a mild folate-deficient population

Clinica Chimica Acta, 2004

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Research paper thumbnail of Metabolic syndrome and coronary artery disease: Is there a gender specific effect

International Journal of Cardiology, 2006

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Impact of Diabetes on Five-Year Outcomes of Patients With Multivessel Coronary Artery Disease

Annals of Thoracic Surgery, 2007

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Research paper thumbnail of NPHS2 R229Q functional variant is associated with microalbuminuria in the general population

Kidney International, 2004

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