Kumar Pradeep, Misra Shubham, Kumar Amit, Faruq Mohammad, Shakya Sunil, Vardhan Gyan, Vivekanandhan Subiah, Srivastava Achal Kumar, Prasad Kameshwar
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
Department of Functional Genomics, Institutes of Genomics and Integrative Biology, New Delhi, India.
Ann Indian Acad Neurol. 2017 Jan-Mar;20(1):5-12. doi: 10.4103/0972-2327.199910.
Transforming growth factor-beta 1 (TGF-β1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population.
A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method.
Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-β1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2-3.8; = 0.006), G800A (OR, 4.4; 95% CI; 2.1-9.3; < 0.001) and T869C (OR, 2.6; 95% CI; 1.5-4.5; = 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D' =0.51, = 0.23).
Our results suggest that TGF-β1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population.
转化生长因子-β1（TGF-β1）是一种多功能多效细胞因子，参与炎症反应和脑血管疾病的发病机制。关于TGF-β1基因多态性与缺血性卒中（IS）风险之间关联的信息有限。本研究旨在探讨TGF-β1基因（C509T、G800A和T869C）多态性及其单倍型与北印度人群IS风险的关联。
共研究了250例IS患者和250例年龄及性别匹配的对照。IS采用急性卒中治疗中Org 10172试验分类法进行分类。采用条件逻辑回归分析计算TGF-β1基因多态性与IS风险之间的关联强度。使用SNaPshot方法进行基因分型。
发现高血压、糖尿病、血脂异常、饮酒、吸烟、卒中家族史、久坐不动的生活方式和低社会经济地位与IS风险相关。C509T、G800A和T869C基因型在IS组和对照组中的分布符合Hardy-Weinberg平衡。调整后的条件逻辑回归分析显示，在显性模型下，TGF-β1 C509T（优势比[OR]，2.1；95%可信区间[CI]：1.2 - 3.8；P = 0.006）、G800A（OR，4.4；95% CI：2.1 - 9.3；P < 0.001）和T869C（OR，2.6；95% CI：1.5 - 4.5；P = 0.001）与IS风险显著相关。单倍型分析显示，C509 - A800 - T869和T509 - G800 - C869单倍型与IS风险增加显著相关。C509T和T869C处于强连锁不平衡状态（D' = 0.51，P = 0.23）。
我们的结果表明，TGF-β1多态性及其单倍型与北印度人群的IS风险显著相关。
