Tumor necrosis factor-alpha (- 308G/A, + 488G/A, - 857C/T and -1031 T/C) gene polymorphisms and risk of ischemic stroke in north Indian population: A hospital based case-control study

Pradeep Kumar; Amit Kumar; Shubham Misra; Ram Sagar; Mohammad Faruq; Varun Suroliya; Subiah Vivekanandhan; Achal Kumar Srivastava; Kameshwar Prasad

doi:10.1016/j.mgene.2015.11.003

Tumor necrosis factor-alpha (- 308G/A, + 488G/A, - 857C/T and -1031 T/C) gene polymorphisms and risk of ischemic stroke in north Indian population: A hospital based case-control study

Meta Gene. 2015 Nov 17:7:34-9. doi: 10.1016/j.mgene.2015.11.003. eCollection 2016 Feb.

Authors

Pradeep Kumar¹, Amit Kumar¹, Shubham Misra¹, Ram Sagar¹, Mohammad Faruq², Varun Suroliya¹, Subiah Vivekanandhan³, Achal Kumar Srivastava¹, Kameshwar Prasad¹

Affiliations

¹ Department of Neurology, All India Institute of Medical Sciences, New Delhi.
² Institutes of Genomics and Integrative Biology, New Delhi.
³ Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi.

Abstract

Background: Genetic factors may play a role in the susceptibility of Ischemic stroke (IS). Previous studies have shown that Tumour necrosis factor-α (TNF-α) gene polymorphisms were associated with the risk of IS in multiple ethnicities. The present case-control study tested the hypothesis that genetic polymorphisms of the TNF-α gene may affect the risk of IS in North Indian population. We investigated the association of four single nucleotide polymorphisms (- 308G/A, + 488G/A, - 857C/T and -1031 T/C) within TNF-α gene promoter and their haplotypes with the risk of IS.

Methods: IS was classified using the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification. Genotyping was performed for 250 IS patients and 250 age- and sex-matched IS free controls by using SNaPshot technique. Multivariate logistic regression was used to control the confounding effects of demographic and risk factor variables. Haplotype analyses were done by using PHASE software and Linkage disequilibrium (LD) analyses were done by using Haploview version 4.2 software.

Results: An independent association between TNF-α + 488G/A (OR = 2.59; 95%CI 1.46 to 4.60; p = 0.001) and -857C/T (OR = 1.77; 95%CI 1.01 to 3.11; p < 0.04) and risk of IS was observed under dominant model. However, no significant association between -308G/A and -1031 T/C gene polymorphisms and risk of IS was observed. Haplotype analysis showed that A308-G488-C857-T1031 haplotypes were significantly associated with the increased risk of IS [OR = 1.66; 95%CI 1.02 to 2.71; p = 0.003]. Strong linkage disequilibrium (LD) was observed for + 488G/A and -857C/T (D' = 0.41, r(2) = 0.004).

Conclusions: Two SNPs (+ 488G/A and -857C/T) of TNF-α gene and their haplotypes are significantly associated with the risk of IS in the population enrolled from North India. Our findings indicate that polymorphisms and haplotypes of TNF-α gene may be used as a genetic marker for identifying individuals at increased risk for developing IS.

Keywords: Cytokine; Inflammatory gene; Ischemic stroke; Single nucleotide polymorphisms; Tumor necrosis factor-alpha.