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rs12196996 是位于基因侧翼内含子的一个多态性，与 circFOXO3 水平和冠心病风险相关。

rs12196996, a polymorphism at the gene flanking intron, is associated with circFOXO3 levels and the risk of coronary artery disease.

机构信息

Institute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. China.

Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, P.R. China.

出版信息

Aging (Albany NY). 2020 Jul 2;12(13):13076-13089. doi: 10.18632/aging.103398.

DOI:10.18632/aging.103398
PMID:32614786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7377899/
Abstract

CircFOXO3 plays an important role in the pathogenesis of coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) at circRNA flanking introns may change its back-splicing and influence circRNA formation. Here, we aimed to investigate the influence of the polymorphisms at the flanking introns on individual susceptibility to CAD. A total of 1185 individuals were included in the case-control study. In a multivariate logistic regression analysis, we determined that the rs12196996 G variant was significantly associated with increased CAD risk (OR = 1.36, = 0.014). A similar trend of the association was observed in the recessive model (OR = 2.57, = 0.003). Stratified analysis revealed a more significant association with CAD risk among younger subjects and non-smokers. Consistent with these results, the haplotype rs12196996G-rs9398171C containing rs12196996G allele was also associated with increased CAD risk (OR = 1.31, = 0.013). Further investigation revealed that the rs12196996 GG genotype was associated with decreased circFOXO3 expression, but not linear FOXO3 levels. Taken together, our data provide the first evidence that the rs12196996 polymorphism at the gene flanking intron is associated with CAD risk in the Chinese Han population, which is probably due to influence circFOXO3 levels.

摘要

环状 RNA FOXO3 在冠状动脉疾病（CAD）的发病机制中起重要作用。环状 RNA 侧翼内含子的单核苷酸多态性（SNP）可能改变其反向剪接并影响环状 RNA 的形成。在这里，我们旨在研究侧翼内含子中的多态性对个体 CAD 易感性的影响。共有 1185 人纳入病例对照研究。在多变量逻辑回归分析中，我们确定 rs12196996G 变体与 CAD 风险增加显著相关（OR=1.36， =0.014）。在隐性模型中观察到类似的关联趋势（OR=2.57， =0.003）。分层分析显示，在年轻患者和非吸烟者中，与 CAD 风险的相关性更为显著。与这些结果一致，含有 rs12196996G 等位基因的 rs12196996G-rs9398171C 单倍型也与 CAD 风险增加相关（OR=1.31， =0.013）。进一步的研究表明，rs12196996 GG 基因型与环状 FOXO3 表达降低相关，但与线性 FOXO3 水平无关。总之，我们的数据首次提供了证据，表明侧翼内含子基因 rs12196996 多态性与中国汉族人群 CAD 风险相关，这可能是由于影响环状 FOXO3 水平所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f2b/7377899/07e0ecbe6ca2/aging-12-103398-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f2b/7377899/14991f4ef685/aging-12-103398-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f2b/7377899/07e0ecbe6ca2/aging-12-103398-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f2b/7377899/14991f4ef685/aging-12-103398-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f2b/7377899/07e0ecbe6ca2/aging-12-103398-g002.jpg

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