Zhang Jingjing, Yu Lihua, Yin Yanying, Lu Qian, Lei Lei, Xiao Jing, Guo Jian, Zhao JingJing, Wang Yanan, He Guoqian, Xu Yanming, He Li
Department of Neurology, West China Hospital, Sichuan University , Chengdu, Sichuan Province, China .
Genet Test Mol Biomarkers. 2013 Nov;17(11):789-93. doi: 10.1089/gtmb.2013.0131. Epub 2013 Aug 14.
Currently, there is a debate regarding the roles of two functional fibrinogen-related variants (rs6050 and rs1800790) and ischemic stroke (IS).
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.
We found that the homozygous minor allele genotype (GG) of rs6050 significantly increased IS risk by 66%, whereas that of rs1800790 reduced risk by 59% (rs6050: odds ratio [OR]=1.660, 95% confidence intervals [CI]: 1.141-2.415, p=0.008; rs1800790: 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; rs1800790: 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 rs1800790) could reduce susceptibility to IS by 35% (OR=0.650, 95% CI: 0.493-0.858, p=0.002).
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 rs1800790 and the haplotype AA lower such risk.
目前，关于两种功能性纤维蛋白原相关变体（rs6050和rs1800790）与缺血性卒中（IS）的作用存在争议。
采用连接检测反应法对1402名受试者（834例病例和568例对照）进行单核苷酸多态性rs6050和rs1800790基因分型。
我们发现，rs6050的纯合次要等位基因基因型（GG）使IS风险显著增加66%，而rs1800790的纯合次要等位基因基因型使风险降低59%（rs6050：比值比[OR]=1.660，95%置信区间[CI]：1.141 - 2.415，p = 0.008；rs1800790：OR = 0.413，95% CI：0.228 - 0.747，p = 0.003）。将IS按三种常见亚型分层后，在大动脉粥样硬化性IS病例中发现了一致的结果（rs系列6050：OR = 2.116，95% CI：1.327 - 3.376，p = 0.002；rs1800790：OR = 0.191，95% CI：0.085 - 0.430，p = 0.000），并且我们还观察到，在心源性栓塞性IS病例中，rs6050的纯合次要等位基因基因型使风险增加86%（OR = 1.859，95% CI：1.243 - 2.782，p = 0.003）。然而，这两个位点与纤维蛋白原水平之间显示出关联悖论。在单倍型分析中，我们发现携带单倍型AA（rs6050的主要等位基因和rs1800790的次要等位基因）的个体对IS的易感性可降低35%（OR = 0.650，95% CI：0.493 - 0.858，p = 0.002）。
我们的研究表明，rs6050的次要等位基因G是一个显著的风险因素，可增加中国汉族人群的IS风险，而rs1800790的次要等位基因A和单倍型AA可降低此类风险。
