Kumar Amit, Misra Shubham, Kumar Pradeep, Sagar Ram, Prasad Kameshwar
Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi, India.
Pulse (Basel). 2017 Jan;4(4):165-171. doi: 10.1159/000449361. Epub 2016 Oct 12.
Stroke is a multifactorial disease influenced by both genetic and environmental factors. The aim of this case-control study was to determine the association between β-fibrinogen C148T (rs1800787) gene polymorphism and susceptibility to ischemic stroke (IS) in a North Indian population.
In the present case-control study, genotyping was performed using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method on 250 IS patients and 250 age- and sex-matched controls. Frequency distributions of genotypes and alleles were compared between the cases and controls by conditional logistic regression.
Hypertension, diabetes, dyslipidemia, low socioeconomic status, and family history of stroke were found to be independent risk factors for IS. The mean age of the cases and controls was 52.83 ± 12.59 and 50.97 ± 12.70 years, respectively. Multivariate logistic regression analysis showed an independent association between β-fibrinogen C148T (rs1800787) polymorphism and risk of IS in dominant (OR = 2.19; 95% CI 1.23-3.90; p = 0.007) and allelic (OR = 1.66; 95% CI 1.19-2.33; p = 0.002) models. Based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, an independent association of small vessel disease with risk of IS was observed in the dominant (OR = 2.09; 95% CI 1.10-3.96; p = 0.02) and allelic (OR = 1.75; 95% CI 1.12-2.75; p = 0.01) models, and a significant association of cardioembolic stroke with risk of IS was seen in the allelic model (OR = 2.11; 95% CI 1.07-4.17; p = 0.02). All the genotype frequencies observed were in accordance with Hardy-Weinberg equilibrium in both cases and controls.
The findings of the present study suggest that polymorphism in the C148T position of the β-fibrinogen gene might be a risk factor for IS mainly for the small vessel disease stroke subtype in a North Indian population. Further, large prospective studies are required to confirm these findings.
中风是一种受遗传和环境因素共同影响的多因素疾病。本病例对照研究的目的是确定北印度人群中β-纤维蛋白原C148T（rs1800787）基因多态性与缺血性中风（IS）易感性之间的关联。
在本病例对照研究中，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对250例IS患者和250例年龄及性别匹配的对照进行基因分型。通过条件逻辑回归比较病例组和对照组之间基因型和等位基因的频率分布。
高血压、糖尿病、血脂异常、低社会经济地位和中风家族史被发现是IS的独立危险因素。病例组和对照组的平均年龄分别为52.83±12.59岁和50.97±12.70岁。多变量逻辑回归分析显示，在显性（OR = 2.19；95% CI 1.23 - 3.90；p = 0.007）和等位基因（OR = 1.66；95% CI 1.19 - 2.33；p = 0.002）模型中，β-纤维蛋白原C148T（rs1800787）多态性与IS风险之间存在独立关联。根据急性中风治疗中Org 10172试验（TOAST）分类，在显性（OR = 2.09；95% CI 1.10 - 3.96；p = 0.02）和等位基因（OR = 1.75；95% CI 1.12 - 2.75；p = 0.01）模型中观察到小血管疾病与IS风险之间存在独立关联，并且在等位基因模型中观察到心源性栓塞性中风与IS风险之间存在显著关联（OR = 2.11；95% CI 1.07 - 4.17；p = 0.02）。在病例组和对照组中观察到的所有基因型频率均符合哈迪-温伯格平衡。
本研究结果表明，β-纤维蛋白原基因C148T位点的多态性可能是北印度人群中IS的一个危险因素，主要针对小血管疾病中风亚型。此外，需要进一步的大型前瞻性研究来证实这些发现。
