title: Association between lymphotoxin alpha (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke in North Indian population: a hospital-based case-control study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Neurology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: a Department of Neurology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: a Department of Neurology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Shubham
authors.initials: S
authors.lastname: Misra
authors.affiliation: b Functional Genomics , Institute of Genomics and Integrative Biology , New Delhi , India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Faruq
authors.affiliation: c Neurosciences Center , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Subiah
authors.initials: S
authors.lastname: Vivekanandhan
authors.affiliation: a Department of Neurology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Achal Kumar
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: a Department of Neurology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Kameshwar
authors.initials: K
authors.lastname: Prasad
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*
chemical_list: D008233:Lymphotoxin-alpha
keywords: cerebrovascular disease; cytokine; intracerebral hemorrhage; ischemic stroke; lymphotoxin alpha; single nucleotide polymorphism; stroke