Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Department of Neurology, Affiliated Yixing People's Hospital of Jiangsu University, People's Hospital of Yixing City, Yixing 214200, China.
Int J Med Sci. 2021 Feb 23;18(8):1840-1847. doi: 10.7150/ijms.45856. eCollection 2021.
High temperature requirement protein A1 (1) was identified as the causative gene of autosomal recessive arteriopathy and associated with lacunar ischemic stroke (IS) in European. This study aimed at evaluating the association of with IS and four tagging single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of 4,098 Chinese. The mRNA level of in 72 IS cases and 72 hypertension controls were measured and compared. In whole population, SNP rs2268350 (C>T) was significantly associated with IS incidence (=0.034). Stratification analysis observed significant association of rs2268350 in male, smoking and drinking populations, rs2672587 (C>G) in smoking and nonsmoking populations and rs3793917 (C>G) in smoking, nonsmoking and nondrinking populations with stroke respectively (<0.05). The additive interaction and multiplicative interaction between rs2268350 and smoking were both of significant (P<0.05) after adjustment for the covariates. There was a cumulated risk of IS among genotypes of rs3793917 (=0.009) and rs2672587 (=0.047) in smoking population. The mRNA level of in non-smokers with rs2268350 CC was significantly higher than smokers with rs2268350 CT/TT (P=0.046) in IS cases. Our findings support that confers the genetic susceptibility to IS and smoking might modify the genetic effect of on IS by suppressing mRNA expression.
高温需求蛋白 A1（1）被鉴定为常染色体隐性动脉病的致病基因，并与欧洲的腔隙性缺血性中风（IS）相关。本研究旨在评估与 IS 的关联，并在一个包含 4098 名中国人的队列中对四个标记单核苷酸多态性（SNP）进行基因分型。测量并比较了 72 例 IS 病例和 72 例高血压对照组中 的 mRNA 水平。在全人群中，SNP rs2268350（C>T）与 IS 发生率显著相关（=0.034）。分层分析观察到 rs2268350 在男性、吸烟和饮酒人群中，rs2672587（C>G）在吸烟和非吸烟人群中，rs3793917（C>G）在吸烟、非吸烟和不饮酒人群中与中风的显著关联（<0.05）。在调整协变量后，rs2268350 与吸烟之间的相加交互作用和相乘交互作用均具有显著性（P<0.05）。在吸烟人群中，rs3793917（=0.009）和 rs2672587（=0.047）的基因型中存在 IS 的累积风险。在 IS 病例中，非吸烟者的 rs2268350 CC 基因型的 表达水平显著高于吸烟者的 rs2268350 CT/TT（P=0.046）。我们的研究结果支持 赋予 IS 的遗传易感性，并且吸烟可能通过抑制 的 mRNA 表达来修饰 对 IS 的遗传效应。
