HLA-DPbeta chain may confer the susceptibility to hepatitis C virus-associated hypertrophic cardiomyopathy.
ABSTRACT 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.
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ABSTRACT: Hepatitis C virus (HCV) is the cause of many different forms of heart disease worldwide, and yet few cardiologists are aware of it as an etiology of heart disease, or its treatment. The burden of HCV-derived heart diseases is global, with a higher prevalence in Asia, Africa, and low- and middle-income countries. Our study showed that in more than 10% of Japanese patients, their cardiomyopathies are associated with HCV infection. More recently, we found in the USA that up to 15% of patients with heart failure with myocarditis have associated HCV infection. In contrast, in China 79% of patients with hepatocellular cancer and 37% of hepatitis C patients have heart disease, as detected by measuring a proven and sensitive biomarker of heart disease, NT-proBNP. In Pakistan, 17% of hepatitis C patients have heart diseases, as measured by this metric.Based on these data, 3% of 6.6 billion (198 million) persons worldwide are infected with HCV, and 17–37% (34–73 million) persons are suffering from HCV-derived heart diseases. These figures may be comparable to the number of patients with hepatitis C. HCV infection causes only hepatitis in some patients, only heart diseases in some patients, and both hepatitis and heart diseases in other patients.A global network is required to establish methods to detect heart diseases caused by infectious agents. Other goals for the network are the expansion of preventive and therapeutic programs in underprivileged countries.CVD Prevention and Control. 01/2009;
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ABSTRACT: Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.World Journal of Gastroenterology 07/2009; 15(24):2960-74. · 2.55 Impact Factor