Purpose: Lymphotoxin alpha (LTA), a proinflammatory cytokine, plays an important role in promoting atherosclerosis which is an independent risk factor for stroke. Recent genetic studies have suggested that polymorphisms in the LTA gene, which affect its expression and biological function, may contribute to the development of stroke. The aim of this case-control study was to determine the association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke.
Methods: Genotyping was determined by using SNaPshot method for 250 ischemic stroke (IS) patients, 250 age and sex matched IS free controls, 100 intracerebral hemorrhage (ICH) patients and 100 age and sex matched ICH free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. The linkage disequilibrium (LD) was analyzed by using HaploView 4.2 software.
Results: The distribution of LTA (-252 A/G and -804 C/A) genotypes was consistent with Hardy-Weinberg equilibrium. Adjusted conditional logistic regression analysis showed no significant association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of both IS and ICH. Based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, a significant association between LTA -252 A/G gene polymorphism and small vessel disease subtype of IS under dominant model (OR, 2.06; 95% CI, 1.03-4.12; p value 0.04) with the risk of IS was observed. No LD was observed for both single nucleotide polymorphisms (SNPs) in north Indian population.
Conclusion: Neither -252 G/A nor -804 C/A polymorphism of the LTA gene was found to be associated with overall stroke as well as any subtype of IS excluding SVD in North Indian population.
Keywords: cerebrovascular disease; cytokine; intracerebral hemorrhage; ischemic stroke; lymphotoxin alpha; single nucleotide polymorphism; stroke.