Association of HLA class II DRB1, DPA1 and DPB1 polymorphism with genetic susceptibility to idiopathic dilated cardiomyopathy in Chinese Han nationality

Abstract

Although the aetiology of idiopathic dilated cardiomyopathy (IDC) remains unclear, many immunological abnormalities involving changes in cell-mediated and humoral immunity may be associated with cardiac impairment in IDC. Autoimmune mechanisms are likely to participate in the pathogenesis of at least a subgroup of IDC and components of the major histocompatibility complex may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, which are highly polymorphic, play an important role in the activating of immune responses and thus control the predisposition for or protection from IDC. This study explores the possible contribution of HLA-DRB and DP polymorphisms to IDC susceptibility. DNA genotyping for HLA-DRB1, DPA1 and DPB1 was performed using polymerase chain reaction-sequencing based typing (PCR-SBT) method in 198 IDC patients and 136 random selected healthy Han ethnic individuals living in Northern China. IDC patients were, sub-grouped into asymptomatics (subgroup A), with arrhythmia (subgroup B) and with overt congestive heart failure (subgroup C) according to the clinical manifestations and electrocardiogram or echocardiographic characteristics. ADP/ATP autoantibody was detected in IDC group by immunoblot analysis. The results revealed that HLA-DR15, -DPB*0601 frequencies were significantly elevated in IDC group compared with normal control. The DPB1*0601 allele in homozygous form or in combination with allele DPB1*2301 or *3901, was found present more often in IDC patients. The predominance of HLA-DR4 allele was observed in subgroup B after stratification. However, the frequency of DPB1*0101 allele increased in the control than in the IDC group. The frequency of HLA-DPB1*0601 allele was significantly higher in IDC patients with positive autoantibody against ADP/ATP carrier of myocardial mitochondria in contrast to those with negative autoantibody. We conclude that HLA-DR4, -DR15, -DPB1*0601 alleles confers susceptibility to, while DPB1*0101 allele confers protection from IDC among individuals of northern Chinese Han nationality. The glutamate at position 69 in the second exon of DPB1*0601, as a key residue for special conformation of HLA-DP, may confer predisposition to IDC. HLA-DR and -DP alleles polymorphisms may serve as genetic markers for IDC and be involved in the regulation of the immune specific response to auto or exterior anti-myocardium antibodies.

• Human leukocyte antigen
• polymorphism
• idiopathic dilated cardiomyopathy
• genetic susceptibility
• autoimmune

Acknowledgements

We greatly acknowledge the collaboration with many colleagues at our institute and at other institutions in this field. Our own work summarized in this paper has been supported by grants of the Harbin Medical University Postgraduate Creation Foundation (2005).