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Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease.

ABSTRACT: An imbalance in sex hormone ratios has been identified in coronary heart disease (CHD), and as a key enzyme in the conversion of androgen to estrogen, aromatase plays an important role in the balance of sex hormone levels. However, there is a paucity of research into the potential roles of aromatase in CHD. In this study, we investigated associations between single-nucleotide polymorphisms (SNPs) in the CYP19 gene, which encodes aromatase, and CHD.We collected 1706 blood samples from CHD patients and control participants and used propensity score matching techniques to match case and control groups with respect to confounding factors. In a final study population, including 596 individuals, we conducted a case-control study to identify associations between three SNPs in CYP19 and CHD using ?(2) or Fisher exact tests, and binary logistic regression analysis. Differences in lipid levels and parameters of echocardiography among individuals with different genotypes were assessed by one-way analysis of variance.The distributions of rs2289105 alleles in the CYP19 gene differed significantly between the CHD and control groups (p = 0.014), and the heterozygote CT genotype was associated with a significantly lower risk of CHD compared to the homozygous wild-type CC genotype (p = 0.0063 and odds ratio = 0.575). However, blood lipid levels and echocardiographic parameters among individuals with different genotypes did not differ between the CHD and control groups.The CT genotype of the rs2289105 polymorphism in the CYP19 gene is associated with a decreased risk of CHD and may be a genetic marker of protection from CHD.

SUBMITTER: Wang B

PROVIDER: S-EPMC4742981 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease.

Wang Bei B Fu Zhen-Yan ZY Ma Yi-Tong YT Huang Ding D Liu Fen F Dong Chun-Lan CL Wang Ting T Meng Ya-Jie YJ

Genetic testing and molecular biomarkers 20151112 1

<h4>Objective</h4>An imbalance in sex hormone ratios has been identified in coronary heart disease (CHD), and as a key enzyme in the conversion of androgen to estrogen, aromatase plays an important role in the balance of sex hormone levels. However, there is a paucity of research into the potential roles of aromatase in CHD. In this study, we investigated associations between single-nucleotide polymorphisms (SNPs) in the CYP19 gene, which encodes aromatase, and CHD.<h4>Methods</h4>We collected 1 ...[more]

PMID: 26562495

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Project description:Ischemic heart disease (IHD) has a genetic predisposition and a number of cardiovascular risk factors are known to be affected by genetic factors. Development of metabolic syndrome and insulin resistance, strongly influenced by lifestyle and environmental factors, frequently occur in subjects with a genetic susceptibility. The definition of genetic factors influencing disease susceptibility would allow to identify individuals at higher risk and thus needing to be closely monitored.To this end, we focused on a complex of soluble-N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), playing an important role in metabolic syndrome and insulin resistance, involved in endothelial dysfunction and heart disease. We assessed if genetic variants of the SNARE genes are associated with IHD.SNAP25 rs363050, Stx-1A rs4717806, rs2293489, and VAMP2 26bp ins/del genetic polymorphisms were analyzed in a cohort of 100 participants who underwent heart surgery; 56 of them were affected by IHD, while 44 were not. A statistical association of plasma glycemia and insulin resistance, calculated as Triglyceride glucose (TyG) index, was observed in IHD (P < .001 and P = .03, respectively) after binomial logistic stepwise regression analysis, adjusted by age, gender, diabetes positivity, waist circumference, and cholesterol plasma level. Among genetic polymorphisms, rs4717806(A) and rs2293489(T), as well as the rs4717806 - rs2293489 (A-T) haplotype were associated with higher risk for IHD (Pc = .02; Pc = .02; P = .04, respectively). Finally, a statistical association of rs4717806(AA) genotype with higher TyG index in IHD patients (P = .03) was highlighted by multiple regression analysis considering log-transformed biochemical parameters as dependent variable and presence of coronary artery disease, age, gender, waist circumference, presence of diabetes as predictors. These results point to a role of the Stx-1A rs4717806 SNP in IHD, possibly due to its influence on Stx-1A expression and, as a consequence, on insulin secretion and glucose metabolism.

Dataset Information

Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease.

Publications

Identification of a CYP19 Gene Single-Nucleotide Polymorphism Associated with a Reduced Risk of Coronary Heart Disease.

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