Najd-Hassan-Bonab Leila, Daneshpour Maryam S, Jafarinia Mojtaba, Akbarzadeh Mahdi, Moazzam-Jazi Maryam, Asgarian Sara, Khalili Davood
Department of Genetics, Marvdasht branch, Islamic Azad University, Marvdasht, Iran.
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Expert Rev Mol Diagn. 2024 Dec 5:1-10. doi: 10.1080/14737159.2024.2436399.
The development of coronary artery disease (CAD) is influenced by sex and genetic factors. Genome-wide association studies (GWAS) have linked genetic loci to CAD, mostly in European populations. The study aims to find sex-related genetic differences in the Iranian population.
We conducted a sex-stratified GWAS with 4519 subjects (1832 males and 2687 females) in the discovery group and 922 subjects (495 males and 427 females) in the confirmation group of an Iranian cohort. We analyzed 9,141,124 variants using a genome-wide complex trait analysis (GCTA) tool.
We detected distinct genetic variants associated with CAD in males: rs34952209 [OR = 1.79; = 5.216E-8], rs1432687863 [OR = 1.95; = 8.477E-8], and in females, rs7314741 [OR = 1.67; = 7.142-8E] positively influenced CAD risk. The CAD-associated SNPs that were obtained have been confirmed using independent samples. Rs3495229 May impact histone mark and Pou2f2 motifs, while rs7314741 in the LEM Domain Containing 3 (LEMD3) promoter may affect a regulatory motif for the STAT transcription factor. According to Roadmap and ENCODE data, Rs1432687863 is a new variant affecting CAD in males, potentially through H3K9me3 in the heart.
Our findings highlight the role of sex-specific genetic differences in CAD development, providing novel insights into disease pathways which is not appropriate using a sex-combined strategy. [Figure: see text].
冠状动脉疾病（CAD）的发展受性别和遗传因素影响。全基因组关联研究（GWAS）已将基因位点与CAD联系起来，主要是在欧洲人群中。本研究旨在发现伊朗人群中与性别相关的遗传差异。
我们在一个伊朗队列的发现组中对4519名受试者（1832名男性和2687名女性）以及在验证组中对922名受试者（495名男性和427名女性）进行了性别分层的GWAS。我们使用全基因组复杂性状分析（GCTA）工具分析了9,141,124个变异。
我们在男性中检测到与CAD相关的不同基因变异：rs34952209 [比值比（OR）= 1.79；P = 5.216E - 8]，rs1432687863 [OR = 1.95；P = 8.477E - 8]，而在女性中，rs7314741 [OR = 1.67；P = 7.142 - 8E]对CAD风险有正向影响。所获得的与CAD相关的单核苷酸多态性（SNP）已使用独立样本进行了验证。Rs3495229可能影响组蛋白标记和Pou2f2基序，而含LEM结构域3（LEMD3）启动子中的rs7314741可能影响信号转导和转录激活因子（STAT）转录因子的调控基序。根据路线图和ENCODE数据，Rs1432687863是一个影响男性CAD的新变异，可能通过心脏中的H3K9me3起作用。
我们的研究结果突出了性别特异性遗传差异在CAD发展中的作用，为使用性别联合策略不合适的疾病途径提供了新的见解。[图：见正文]
