CYP3A4 and CYP11A1 variants are risk factors for ischemic stroke: a case control study

Ning Gao,Ying Xia,Ling Gao,Han Luo,Hong Tang,Guolong Tu

doi:10.1186/s12883-020-1628-4

Ning Gao, Ying Xia + Show 4 more

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https://doi.org/10.1186/s12883-020-1628-4

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Abstract

BackgroundThis study aimed to investigate the roles of CYP3A4 and CYP11A1 variants in ischemic stroke (IS) susceptibility among the Han Chinese population.MethodsFour hundred seventy-seven patients with IS and 493 healthy controls were enrolled. Seven single-nucleotide polymorphisms (SNPs) of CYP3A4 and CYP11A1 were genotyped by Agena MassARRAY. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression adjusted for age and gender.ResultsWe found that CYP3A4 rs3735451 (OR = 0.81, p = 0.039) and rs4646440 (OR = 0.72, p = 0.021) polymorphisms decreased the risk of IS. CYP3A4 rs4646440 (OR = 0.74, p = 0.038) and CYP11A1 rs12912592 (OR = 1.58, p = 0.034) polymorphisms were correlated with IS risk in males. CYP3A4 rs3735451 (OR = 0.63, p = 0.031) and rs4646440 (OR = 0.57, p = 0.012) possibly weaken the IS susceptibility at age > 61 years. Besides, CYP3A4 rs4646437 (OR = 0.59, p = 0.029), CYP11A1 rs12912592 (OR = 1.84, p = 0.017) and rs28681535 (OR = 0.66, p = 0.038) were associated with IS risk at age ≤ 61 years. CYP11A1 rs28681535 TT genotype was higher high-density lipoprotein cholesterol level than the GT and GG genotype (p = 0.027).ConclusionsOur findings indicated that rs3735451, rs4646440, rs4646437 in CYP3A4 and rs28681535 in CYP11A1 might be protective factors for IS, while CYP11A1 rs12912592 polymorphism be a risk factor for IS in Chinese Han population.

Highlights

This study aimed to investigate the roles of CYP3A4 and CYP11A1 variants in ischemic stroke (IS) susceptibility among the Han Chinese population
We found that CYP3A4 rs4646440 was associated with a decreased risk under the additive model (OR = 0.74, 95% confidence intervals (CI): 0.56–0.98, p = 0.038), and showed a marginal p value in allele model (OR = 0.76, 95% CI: 0.58–1.00, p = 0.050) among males, which indicated insufficient evidence for claiming an association
We found that CYP3A4 and CYP11A1 polymorphisms were significantly associated with the risk of IS

Summary

Introduction

This study aimed to investigate the roles of CYP3A4 and CYP11A1 variants in ischemic stroke (IS) susceptibility among the Han Chinese population. The incidence of stroke is estimated to be more than 2 million people and more than 1 million people die from stroke-related causes every year in the Chinese population [1]. The pathophysiological causes of IS are unclear, Cytochrome P450s (CYPs) is a group of complexes and structurally related enzymes with diverse metabolic and biosynthetic activities. CYP epoxygenases is metabolizing arachidonic acid (AA) to biologically active epoxyeicosatrienoic acids (EETs), which exert vascular relaxation effects and have diverse protective roles in the cardiovascular system [9]. CYP3A4 gene, located on chromosome 7q21.1, is a member of the CYP3A gene family, which participates in metabolizing arachidonic acid (AA) into epoxyeicosatrienoic acids (EETs) [12].

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