ALDH2、ADCY3 和 BCMO1 多态性与生活方式诱导的特征与中国汉族人群 CAD 风险相关。
ALDH2, ADCY3 and BCMO1 polymorphisms and lifestyle-induced traits are jointly associated with CAD risk in Chinese Han people.
机构信息
School of Public Health, Hangzhou Normal University, Hangzhou 310000, China.
Wu Yun Shan Hospital, Hangzhou 31000, China.
出版信息
Gene. 2022 Jan 10;807:145948. doi: 10.1016/j.gene.2021.145948. Epub 2021 Sep 2.
BACKGROUNDS
To investigate associations of genetic and environmental factors with coronary artery disease (CAD), we collected medical reports, lifestyle details, and blood samples of 2113 individuals, and then used the polymerase chain reaction (PCR)-ligase detection reaction (LDR) to genotype the targeted 102 SNPs.
METHODS
We adopted elastic net algorithm to build an association model that considered simultaneously genetic and lifestyle/clinical factors associated with CAD in Chinese Han population.
RESULTS
In this study, we developed an all covariates-based model to explain the risk of CAD, which incorporated 8 lifestyle/clinical factors and a gene-score variable calculated from 3 significant SNPs (rs671, rs6751537 and rs11641677), attaining an area under the curve (AUC) value of 0.71. It was found that, in terms of genetic variants, the AA genotype of rs671 in the additive (adjusted odds ratio (OR) = 2.51, p = 0.008) and recessive (adjusted OR = 2.12, p = 0.021) models, the GG genotype of rs6751537 in the additive (adjusted OR = 3.36, p = 0.001) and recessive (adjusted OR = 3.47, p = 0.001) models were associated with increased risk of CAD, while GG genotype of rs11641677 in additive model (adjusted OR = 0.39, p = 0.044) was associated with decreased risk of CAD. In terms of lifestyle/clinical factors, the history of hypertension (unadjusted OR = 2.37, p < 0.001) and dyslipidemia (unadjusted OR = 1.82, p = 0.007), age (unadjusted OR = 1.07, p < 0.001) and waist circumference (unadjusted OR = 1.02, p = 0.05) would significantly increase the risk of CAD, while height (unadjusted OR = 0.97, p = 0.006) and regular intake of chicken (unadjusted OR = 0.78, p = 0.008) reduced the risk of CAD. A significantinteraction was foundbetween rs671 and dyslipidemia (the relative excess risk due to interaction (RERI) = 3.36, p = 0.05).
CONCLUSION
In this study, we constructed an association model and identified a set of SNPs and lifestyle/clinical risk factors of CAD in Chinese Han population. By considering both genetic and non-genetic risk factors, the built model may provide implications for CAD pathogenesis and clues for screening tool development in Chinese Han population.
背景
为了研究遗传和环境因素与冠心病（CAD）的关联，我们收集了 2113 名个体的医疗报告、生活方式细节和血液样本，并使用聚合酶链反应（PCR）-连接酶检测反应（LDR）对靶向的 102 个 SNP 进行基因分型。
方法
我们采用弹性网络算法构建了一个关联模型，该模型同时考虑了与中国汉族人群 CAD 相关的遗传和生活方式/临床因素。
结果
在这项研究中，我们开发了一个基于所有协变量的模型来解释 CAD 的风险，该模型纳入了 8 个生活方式/临床因素和一个由 3 个显著 SNP(rs671、rs6751537 和 rs11641677)计算得出的基因评分变量，获得了 0.71 的曲线下面积(AUC)值。结果表明，就遗传变异而言，rs671 的 AA 基因型在加性模型（调整后的比值比(OR)为 2.51，p=0.008）和隐性模型（调整后的 OR 为 2.12，p=0.021）中，rs6751537 的 GG 基因型在加性模型（调整后的 OR 为 3.36，p=0.001）和隐性模型（调整后的 OR 为 3.47，p=0.001）中与 CAD 风险增加相关，而 rs11641677 的 GG 基因型在加性模型中（调整后的 OR 为 0.39，p=0.044）与 CAD 风险降低相关。就生活方式/临床因素而言，高血压史（未调整的 OR 为 2.37，p<0.001）和血脂异常（未调整的 OR 为 1.82，p=0.007）、年龄（未调整的 OR 为 1.07，p<0.001）和腰围（未调整的 OR 为 1.02，p=0.05）显著增加 CAD 的风险，而身高（未调整的 OR 为 0.97，p=0.006）和定期摄入鸡肉（未调整的 OR 为 0.78，p=0.008）降低 CAD 的风险。rs671 与血脂异常之间存在显著的交互作用（交互归因风险增加（RERI）为 3.36，p=0.05）。
结论
在这项研究中，我们构建了一个关联模型，并确定了一组与中国汉族人群 CAD 相关的 SNP 和生活方式/临床危险因素。通过同时考虑遗传和非遗传风险因素，所构建的模型可能为 CAD 的发病机制提供了启示，并为中国汉族人群的筛查工具开发提供了线索。
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