Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese

Biochem Biophys Res Commun. 1999 Aug 2;261(2):332-9. doi: 10.1006/bbrc.1999.1036.

Abstract

To reveal genetic risk factors of nonfamilial idiopathic cardiomyopathy (IDC) in Japanese, polymorphisms in the SOD2 and HLA-DRB1 genes were investigated in 86 patients and 380 healthy controls. There was a significant excess of homozygotes for the V allele [Val versus Ala (A allele), a polymorphism in the leader peptide of manganese superoxide dismutase at position 16] of the SOD2 gene in the patients compared with the controls (87.2% versus 74.7%, odds ratio = 2.30, p = 0.013, pc < 0.03), and a significant increase in the frequency of HLA-DRB1*1401 in the patients was confirmed (14.0% vs 4.5%, odds ratio = 3.46, p = 0.001, pc < 0.03). A two-locus analysis suggested that these two genetic markers (SOD2-VV genotype and DRB1*1401) may play a synergistic role in controlling the susceptibility to nonfamilial IDC. In addition, processing efficiency of Val-type SOD2 leader peptide in the presence of mitochondria was siginificantly lower than that of the Ala-type by 11 +/- 4%, suggesting that this lower processing efficiency was in part an underlying mechanism of the association between the SOD2-VV genotype and nonfamilial IDC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Base Sequence
  • Cardiomyopathy, Dilated / enzymology
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / immunology
  • Case-Control Studies
  • DNA Primers / genetics
  • Female
  • Genetic Markers
  • Genotype
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Humans
  • Japan
  • Male
  • Mice
  • Middle Aged
  • Mitochondria / metabolism
  • Odds Ratio
  • Oligonucleotide Probes / genetics
  • Polymorphism, Genetic*
  • Protein Processing, Post-Translational
  • Protein Sorting Signals / genetics
  • Protein Sorting Signals / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Risk Factors
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism

Substances

  • DNA Primers
  • Genetic Markers
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Oligonucleotide Probes
  • Protein Sorting Signals
  • Recombinant Fusion Proteins
  • Superoxide Dismutase