FLNA 和 FLNB 变异与差异表达的 mRNA 一起导致高血压和中风的易感性。

The variants at FLNA and FLNB contribute to the susceptibility of hypertension and stroke with differentially expressed mRNA.

机构信息

Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.

Department of Neurology, Affiliated Yixing People's Hospital of Jiangsu University, People's Hospital of Yixing City, Yixing, China.

出版信息

Pharmacogenomics J. 2021 Aug;21(4):458-466. doi: 10.1038/s41397-021-00222-y. Epub 2021 Mar 1.

DOI:10.1038/s41397-021-00222-y

PMID:33649519

Abstract

BACKGROUND

Filamin A and filamin B were involved in vascular development and remodeling. Herein, it is important to explore the associations of FLNA and FLNB variants with hypertension and stroke.

METHODS

The associations of two single-nucleotide polymorphisms (SNPs) at FLNA and five SNPs at FLNB with hypertension and stroke were examined in two case-control studies and a cohort study in Chinese Han population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by Logistic and Cox regression analysis respectively. In addition, filamin B, FLNA and FLNB mRNA expression were measured.

RESULTS

In the case-control study of hypertension, FLNA rs2070816 (CT + TT vs. CC) and rs2070829 (CG + GG vs. CC) were significantly associated with hypertension in <55 years group (OR = 1.338, P = 0.018; OR = 1.615, P = 0.005) and FLNB rs839240 (AG + GG vs. AA) was significantly associated with hypertension in females (OR = 0.828, P = 0.041) and nonsmokers (OR = 0.829, P = 0.020). In the follow-up study, rs2070829 GG genotype carriers presented a higher risk of hypertension than CC/CG in males (HR = 1.737, P = 0.014) and smokers (HR = 1.949, P = 0.012). In the case-control study of stroke, FLNB rs1131356 variation was significantly associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH), ORs of additive model were 1.342 and 1.451, with P values of 0.001 and 0.007. The FLNA transcript 2, FLNB transcript 3, transcript 4 mRNA, and filamin B expression levels were significantly different between IS cases and hypertension controls and among the genotypes of rs839240 in hypertensive individuals (P < 0.05).

CONCLUSIONS

Our findings support the genetic contribution of FLNA and FLNB to hypertension, and stroke with differentially mRNA expression.

摘要

背景

细丝蛋白 A 和细丝蛋白 B 参与血管发育和重塑。在此，探讨 FLNA 和 FLNB 变异与高血压和中风的关联非常重要。

方法

在汉族人群的两项病例对照研究和一项队列研究中，检测了 FLNA 上的两个单核苷酸多态性 (SNP) 和 FLNB 上的五个 SNP 与高血压和中风的关联。通过 Logistic 和 Cox 回归分析分别估计风险为比值比 (OR) 和风险比 (HR)。此外，还测量了细丝蛋白 B、FLNA 和 FLNB 的 mRNA 表达。

结果

在高血压病例对照研究中，FLNA rs2070816（CT+TT 与 CC）和 rs2070829（CG+GG 与 CC）在<55 岁组中与高血压显著相关（OR=1.338，P=0.018；OR=1.615，P=0.005），FLNB rs839240（AG+GG 与 AA）在女性（OR=0.828，P=0.041）和非吸烟者（OR=0.829，P=0.020）中与高血压显著相关。在随访研究中，rs2070829 GG 基因型携带者在男性（HR=1.737，P=0.014）和吸烟者（HR=1.949，P=0.012）中患高血压的风险高于 CC/CG。在中风病例对照研究中，FLNB rs1131356 变异与缺血性中风（IS）和脑出血（ICH）显著相关，加性模型的 OR 分别为 1.342 和 1.451，P 值分别为 0.001 和 0.007。IS 病例与高血压对照组以及高血压个体 rs839240 基因型之间的 FLNA 转录本 2、FLNB 转录本 3、转录本 4 mRNA 和细丝蛋白 B 的表达水平存在显著差异（P<0.05）。