title: 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.
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.
authors: Department of Neurology, All India Institute of Medical Sciences, New Delhi.
authors: Pradeep
authors: P
authors: Kumar
authors: Department of Neurology, All India Institute of Medical Sciences, New Delhi.
authors: Amit
authors: A
authors: Kumar
authors: Department of Neurology, All India Institute of Medical Sciences, New Delhi.
authors: Shubham
authors: S
authors: Misra
authors: Department of Neurology, All India Institute of Medical Sciences, New Delhi.
authors: Ram
authors: R
authors: Sagar
authors: Institutes of Genomics and Integrative Biology, New Delhi.
authors: Mohammad
authors: M
authors: Faruq
authors: Department of Neurology, All India Institute of Medical Sciences, New Delhi.
authors: Varun
authors: V
authors: Suroliya
authors: Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi.
authors: Subiah
authors: S
authors: Vivekanandhan
authors: Department of Neurology, All India Institute of Medical Sciences, New Delhi.
authors: Achal Kumar
authors: AK
authors: Srivastava
authors: Department of Neurology, All India Institute of Medical Sciences, New Delhi.
authors: Kameshwar
authors: K
authors: Prasad
keywords: Cytokine; Inflammatory gene; Ischemic stroke; Single nucleotide polymorphisms; Tumor necrosis factor-alpha