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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

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HLA-DPbeta chain may confer the susceptibility to hepatitis C virus-associated hypertrophic cardiomyopathy

D Shichi1, A Matsumori, T K Naruse

  • 1Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

International Journal of Immunogenetics
|January 12, 2008
PubMed

Insights

Certain human leucocyte antigen (HLA) gene variants, specifically DPB1*0401 and DPB1*0901, are linked to an increased risk of developing hepatitis C virus-associated hypertrophic cardiomyopathy (HCV-HCM). These findings suggest a role for HLA-DP molecules in the progression of this heart condition following HCV infection.

Area of Science:

  • Immunogenetics
  • Cardiology
  • Virology

Background:

  • Hypertrophic cardiomyopathy (HCM) is a heart muscle disease.
  • Hepatitis C virus (HCV) infection is a potential cause of HCM, but the underlying mechanisms are unclear.
  • Human leucocyte antigen (HLA) genes influence viral infection outcomes.

Purpose of the Study:

  • To investigate the association between HLA gene polymorphisms and the pathogenesis of HCV-associated HCM (HCV-HCM).

Main Methods:

  • A case-control study was conducted with 38 HCV-HCM patients and 132 healthy controls.
  • Polymorphisms in seven classical and two non-classical HLA genes were analyzed.

Main Results:

  • DPB1*0401 was associated with increased risk of HCV-HCM in a dominant model (P < 0.028, OR = 3.94).
  • DPB1*0901 was associated with increased risk of HCV-HCM in a recessive model (P < 0.007, OR = 9.85).
  • Differences in susceptible residue combinations within the HLA-DP beta chain's peptide-binding pocket may explain the varying risks.

Conclusions:

  • Specific HLA-DP alleles may predispose HCV-infected individuals to developing HCM.
  • The peptide-binding specificity of HLA-DP molecules might play a role in HCV-HCM pathogenesis.

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