title: Association of tumor necrosis factor-α and matrix metalloproteinase-3 gene variants with stroke.
abstract: OBJECTIVE
  There is increasing evidence that the genetic variation in the genes coding for pro-inflammatory markers and matrix metalloproteinase may play an important role in the pathogenesis of various human diseases including stroke. The aim of this study was to evaluate the association of genetic variants within the genes encoding tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3), with stroke.
  
  
  METHODS
  Five hundred and twenty-five ischemic stroke patients and 500 age- and sex-matched controls were included in this study. We analyzed +488 G/A polymorphism in TNF-α gene and -1612 5A/6A polymorphism in MMP-3 gene. The genotypes were determined by Amplification Refractory Mutation System PCR. The strength of association between genotypes and stroke was measured by the odds ratio with 95% confidence interval (CI) and chi-squared analysis.
  
  
  RESULTS
  Allelic and genotypic frequencies of TNF-α G/A polymorphism differed significantly between patients and healthy controls (P < 0.001). A stepwise logistic regression analysis confirmed these findings (P < 0.001). Further, evaluating the association of this polymorphism with stroke subtypes, we found significant association with intracranial large artery atherosclerosis, extracranial large artery atherosclerosis, and stroke of undetermined etiology. As far as MMP-3-1612 5A/6A polymorphism is concerned, there was no significant difference in genotypic distribution and allelic frequency between the patients and healthy controls (P = 0.5 and 0.9, respectively). We tested the gene-gene interaction between TNF-α and MMP-3 genes using the logistic regression model. However, there was no evidence for a gene-gene interaction between TNF-α and MMP-3.
  
  
  CONCLUSIONS
  TNF-α +488 G/A variant is an important risk factor for ischemic stroke in the South Indians from Andhra Pradesh, whereas MMP-3-1612 5A/6A polymorphism is not associated with stroke in the same population.
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India.
authors.forename: A
authors.initials: A
authors.lastname: Munshi
authors.forename: K
authors.initials: K
authors.lastname: Rajeshwar
authors.forename: S
authors.initials: S
authors.lastname: Kaul
authors.forename: A
authors.initials: A
authors.lastname: Al-Hazzani
authors.forename: A A
authors.initials: AA
authors.lastname: Alshatwi
authors.forename: G
authors.initials: G
authors.lastname: Shafi
authors.forename: N
authors.initials: N
authors.lastname: Balakrishna
authors.forename: A
authors.initials: A
authors.lastname: Jyothy
mesh_terms: D015897:Comorbidity; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D020293:Vasculitis, Central Nervous System / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3