HLA-DPbeta chain may confer the susceptibility to hepatitis C virus-associated hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a heart muscle disease characterized by hypertrophy and diastolic dysfunction of cardiac ventricles. It is suggested that one possible aetiology of HCM is the hepatitis C virus (HCV) infection, but molecular mechanisms underlying development of HCV-associated HCM (HCV-HCM) remains unknown. Because the human leucocyte antigen (HLA) molecule is involved in the control of progression/suppression of viral infection, extensive HLA allelic diversity may modulate the post-infectious course of HCV and pathogenesis of HCV-HCM. Here we undertook a case-control study with 38 patients with HCV-HCM and 132 unrelated healthy controls to reveal the potential impact of polymorphisms in seven classical and two non-classical HLA genes on the pathogenesis of HCV-HCM. It was found that DPB1*0401 and DPB1*0901 were significantly associated with increased risk to HCV-HCM in dominant model (P < 0.028, OR = 3.94, 95% confidence interval (CI) = 1.19, 13.02) and in recessive model (P < 0.007, OR = 9.85, 95% CI = 1.83, 53.04), respectively. The disparity in the gene-dose effect by two susceptible DPB1 alleles may be attributable to the difference between the susceptible (36 A and 55 A) and resistant (8L, 9F, 11G, 57E and 76M) residue-combination consisting of DPbeta anchor pocket for antigenic peptide-binding. These results implied that the HLA-DP molecules with specificity pocket appropriate for HCV antigen(s) might confer the progressive process of HCM among the HCV-infected individuals.
Shichi
D
D
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Matsumori
A
A
Naruse
T K
TK
Inoko
H
H
Kimura
A
A
D000956:Antigens, Viral / Q000276:immunology; D044466:Asian People / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006682:HLA-DP Antigens / Q000737:chemistry / Q000235:genetics*; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology; D006801:Humans; D011110:Polymorphism, Genetic
D000956:Antigens, Viral; D006682:HLA-DP Antigens