Genotypes and haplotypes predisposing to myocardial infarction: a multilocus case-control study

Martin D Tobin, Peter S Braund, Paul R Burton, John R Thompson, Richard Steeds, Kevin Channer, Suzanne Cheng, Klaus Lindpaintner, Nilesh J Samani

Research output: Contribution to journalArticle (Academic Journal)peer-review

129 Citations (Scopus)

Abstract

AIM: To identify polymorphisms and haplotypes in candidate genes that predispose to myocardial infarction (MI) using a multilocus approach.

METHODS AND RESULTS: 1052 subjects, comprising 547 acute MI cases and 505 controls were studied. The association between MI and 58 SNPs in 35 candidate genes (generating 61 016 individual genotypes), and between MI and estimated haplotypes at 14 loci encompassing 16 genes was investigated. Two individual gene variants and haplotypes at two loci showed statistical association with MI. The alpha-adducin 460trp variant (OR 0.73, 95% CI 0.59-0.91, P=0.006) and the cholesteryl ester transfer protein -629A variant (OR 0.82, 95% CI 0.68-0.97, P=0.025) were both associated with a significant protective effect on MI, as was the paraoxonase 1/paraoxonase 2 haplotype comprising met55 and gln192 in paraoxonase 1 and cys311 in paraoxonase 2 (OR 0.52, 95% CI 0.39-0.77, P=0.001). The apolipoprotein C III haplotypes CCTTCG and ATCCCG at positions -641*-482*-455*1100*3175*3206 were associated with an increased risk of MI, odds ratios 1.41 (95% CI 1.06-1.76, P=0.023) and 1.71 (95% CI 1.28-2.14, P=0.038), respectively.

CONCLUSIONS: We report associations of two polymorphisms and haplotypes at two loci with risk of MI that warrants testing in future studies. Furthermore, we demonstrate the application of a multilocus assay in the setting of a large association study and the additional benefit gained from the study of haplotypes to identify variants influencing risk of coronary heart disease.

Original languageEnglish
Pages (from-to)459-467
Number of pages9
JournalEuropean Heart Journal
Volume25
Issue number6
DOIs
Publication statusPublished - Mar 2004

Keywords

  • Case-Control Studies
  • Confounding Factors (Epidemiology)
  • Coronary Stenosis
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction
  • Polymorphism, Genetic
  • Risk Factors

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