Department of Cardiology, Zhejiang Hospital, Hangzhou, 310013, Zhejiang Province, China.
Department of Neurology, Zhejiang Hospital, Hangzhou, 310013, Zhejiang Province, China.
Sci Rep. 2017 Dec 13;7(1):17517. doi: 10.1038/s41598-017-17537-1.
Previous work has suggested that ischemic stroke (IS) may be more likely to occur in individuals with a genetic predisposition. In this study, we investigated the potential association of IS-relevant genetic risk factors with cardioembolic stroke (CES) in atrial fibrillation (AF) patients with low CHA2DS2-VaSc score. Genotyping was performed using the GenomeLab SNPstream genotyping platform for five IS-relevant SNPs (MMP-9 C1562T, ALOX5AP SG13S114A/T, MTHFR 677 C/T, FGB 455 G/A, and eNOS G298A) in 479 AF patients with CES and 580 age and sex-matched AF patients without CES. The multivariate analysis adjusted for potential confounders and demonstrated that FGB 455 G/A was independently associated with increased risk of CES in AF patients and the significance remained after Bonferroni correction in the additive, dominant, and recessive models with ORs of 1.548 (95% CI: 1.251-1.915, P = 0.001), 1.588 (95% CI: (1.226-2.057, P = 0.003), and 2.394 (95% CI: 1.357-4.223, P = 0.015), respectively. Plasma fibrinogen levels were significantly higher in patients with the A allele compared with patients with genotype of GG (3.29 ± 0.38 mg/dl vs. 2.87 ± 0.18 mg/dl, P < 0.001). We found for the first time that the A allele of FGB 455 G/A was a risk factor for CES in AF patients, probably by elevating the level of plasma fibrinogen.
先前的研究表明，遗传易感性可能会增加个体发生缺血性卒中（IS）的风险。在这项研究中，我们调查了与 IS 相关的遗传风险因素与低 CHA2DS2-VaSc 评分的心房颤动（AF）患者中心源性栓塞性卒中（CES）的潜在关联。使用 GenomeLab SNPstream 基因分型平台对 479 例 CES 的 AF 患者和 580 例年龄和性别匹配的无 CES 的 AF 患者进行了五个与 IS 相关的 SNP（MMP-9 C1562T、ALOX5AP SG13S114A/T、MTHFR 677C/T、FGB 455G/A 和 eNOS G298A）的基因分型。多变量分析调整了潜在的混杂因素，并表明 FGB 455G/A 与 AF 患者 CES 风险增加独立相关，并且在加性、显性和隐性模型中，经 Bonferroni 校正后，OR 值分别为 1.548（95%CI：1.251-1.915，P=0.001）、1.588（95%CI：1.226-2.057，P=0.003）和 2.394（95%CI：1.357-4.223，P=0.015）。与 GG 基因型的患者相比，携带 A 等位基因的患者的血浆纤维蛋白原水平显著升高（3.29±0.38mg/dl 比 2.87±0.18mg/dl，P<0.001）。我们首次发现 FGB 455G/A 的 A 等位基因是 AF 患者 CES 的危险因素，可能通过升高血浆纤维蛋白原水平。
