Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and PCSK2 with myocardial infarction in Japanese individuals

Atherosclerosis. 2010 Jun;210(2):468-73. doi: 10.1016/j.atherosclerosis.2009.11.050. Epub 2009 Dec 5.

Abstract

Objective: The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in Japanese individuals.

Methods: The study population comprised 5014 Japanese individuals, including 1444 subjects with MI and 3570 controls. The 150 polymorphisms examined in the present study were selected by a genome-wide association study for ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix), and were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.

Results: An initial screen by the chi-square test revealed that the A-->G polymorphism of SEMA3F (rs12632110), the C-->T polymorphism of CLEC16A (rs9925481), the A-->G polymorphism of LAMA3 (rs12373237), and the C-->G polymorphism of PCSK2 (rs6080699) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the A-->G polymorphism of SEMA3F (dominant model; P=0.0014; odds ratio, 0.76), the C-->T polymorphism of CLEC16A (dominant model; P=0.0009; odds ratio, 0.75), the A-->G polymorphism of LAMA3 (recessive model; P=0.0099; odds ratio, 0.80), and the C-->G polymorphism of PCSK2 (recessive model; P=0.0155; odds ratio, 1.19) were significantly (P<0.05) associated with the prevalence of MI.

Conclusion: Determination of these genotypes may prove informative for assessment of the genetic risk for MI in Japanese individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / genetics
  • Coronary Artery Disease / genetics
  • Female
  • Gene Expression Regulation*
  • Genetic Variation*
  • Humans
  • Japan
  • Laminin / genetics*
  • Lectins, C-Type / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Monosaccharide Transport Proteins / genetics*
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / genetics*
  • Nerve Tissue Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Proprotein Convertase 2 / genetics*

Substances

  • CLEC16A protein, human
  • Laminin
  • Lectins, C-Type
  • Membrane Proteins
  • Monosaccharide Transport Proteins
  • Nerve Tissue Proteins
  • SEMA3F protein, human
  • laminin alpha 3
  • Proprotein Convertase 2