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

Abstract

Objective: 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. Methods: 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 v 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. Results: 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. Conclusions: 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.

Aromatase ( CYP19A1 ) gene variants, sex steroid levels, and late‐life depression

“…The TT minor homozygote was associated with an increased risk compared to CC or TC but the confidence intervals were large due to the small numbers. Given the potential genetic associations between CYP19A1 and age-related pathologies Shay et al, 2018;Song et al, 2019;Wang et al, 2016;Westberg & Eriksson, 2008), it seems conceivable that certain genes may be specifically associated with late-life depression. No significant associations were found with the three other SNPs they investigated, including rs749292.…”

“…Associations between CYP19A1 polymorphisms and DEP were assessed using logistic regression adjusted for age. Multivariate models further adjusted for health-related variables, namely cognitive impairment, body mass index, and cardiovascular pathologies, as well as history of major depression and anxiety disorder, due to their association with prevalent DEP (p < .15) and/or the potential association with CYP19A1 polymorphisms (Baghaei et al, 2003;Kravitz, Meyer, et al, 2006b;Rosenfeld et al, 2018;Shay et al, 2018;Wang et al, 2016). Given the potentially unique etiology of late-life depression, including the influence of sex steroids, stratified analysis was undertaken to determine whether a history of depression influenced the associations.…”

“…For women, hormonal fluctuations throughout reproductive life, especially at menopause, can also result in mood disorder (Ancelin et al, 2007). Given the potential genetic associations between CYP19A1 and age-related pathologies Shay et al, 2018;Song et al, 2019;Wang et al, 2016;Westberg & Eriksson, 2008), it seems conceivable that certain genes may be specifically associated with late-life depression.…”

“…Such effect may actually occur in up to 50% of all gene association studies, particularly in Europeans (Comings & MacMurray, 2000). Heterosis has been reported with certain CYP19A1 polymorphisms for testosterone level (Sowers et al, 2006), estradiol decline (Sowers et al, 2011), Alzheimer's disease (Song et al, 2019), coronary heart disease (Wang et al, 2016), as well as endometriosis in Caucasian but not Asian women (Yi, Yang, Lan, & Xi, 2016 (Comings & MacMurray, 2000). Another explanation is based on an inverted U-shaped response curve in which either too little or too much gene expression is deleterious, with optimal gene expression occurring in heterozygotes.…”

“…Multivariate models further adjusted for health-related variables, namely cognitive impairment, body mass index, and cardiovascular pathologies, as well as history of major depression and anxiety disorder, due to their association with prevalent DEP (p < .15) and/or the potential association with CYP19A1 polymorphisms (Baghaei et al, 2003;Kravitz, Meyer, et al, 2006b;Rosenfeld et al, 2018;Shay et al, 2018;Wang et al, 2016). Multivariate models further adjusted for health-related variables, namely cognitive impairment, body mass index, and cardiovascular pathologies, as well as history of major depression and anxiety disorder, due to their association with prevalent DEP (p < .15) and/or the potential association with CYP19A1 polymorphisms (Baghaei et al, 2003;Kravitz, Meyer, et al, 2006b;Rosenfeld et al, 2018;Shay et al, 2018;Wang et al, 2016).…”