Association Between Two Functional Fibrinogen-Related Polymorphisms and Ischemic Stroke: A Case-Control Study

摘要

Objectives: Currently, there is a debate regarding the roles of two functional fibrinogen-related variants (rs6050 and rsl800790) and ischemic stroke (IS). Materials and Methods: A total of 1402 subjects (834 cases and 568 controls) were genotyped for single-nucleotide polymorphisms rs6050 and rs1800790 with the ligation detection reaction method. Results: We found that the homozygous minor allele genotype (GG) of rs6050 significantly increased IS risk by 66%, whereas that of rsl800790 reduced risk by 59% (rs6050: odds ratio [OR] = 1.660, 95% confidence intervals [CI]: 1.141-2.415, p=0.008; rsl800790: OR=0.413, 95% CI: 0.228-0.747, p = 0.003). After stratifying IS by three common subtypes, consistent results were found in IS cases with large-artery atherosclerosis (rs6050: OR=2.116, 95% CI: 1.327-3.376, p = 0.002; rsl800790: OR = 0.191, 95% CI: 0.085-0.430, p =0.000), and we also observed that the homozygous minor allele genotype of rs6050 increased risk by 86% in IS cases with cardioembolism (OR=1.859, 95% CI: 1.243-2.782, p = 0.003). However, a paradox of association was shown between these two sites and fibrinogen levels. In haplotype analysis, we found that those with haplotype AA (major allele of rs6050 and minor allele of rsl800790) could reduce susceptibility to IS by 35% (OR=0.650, 95% CI: 0.493-0.858, p=0.002). Conclusion: Our study suggested that minor allele G of rs6050 is a significant risk factor, which can increase IS risk in the Chinese Han population, while minor allele A of rsl800790 and the haplotype AA lower such risk.