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  • Title: Relationship between HLA-DQA1 polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy.
    Author: Liu W, Li WM, Sun NL.
    Journal: Chin Med J (Engl); 2004 Oct; 117(10):1449-52. PubMed ID: 15498363.
    Abstract:
    BACKGROUND: Autoimmune mechanisms are likely to participate in the pathogenesis of subgroup of idiopathic dilated cardiomyopathy (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, especially highly polymorphic HLA-DQ genes, play an important role in the activation of immune responses, and thus control the predisposition for or protect from IDC. This study was conducted to investigate the HLA-DQA1 allele polymorphisms in IDC patients and to explore the underlying immunological mechanism and the hereditary susceptibility to IDC. METHODS: The polymerase chain reaction sequence-specific primers (PCR-SSP) technique was used to analyze the polymorphisms in the second exon of DQA1 in three groups: 72 IDC patients diagnosed according to the criteria of World Health Organization (IDC group); 100 end-stage heart failure patients suffering from a disease of known etiology (HF group); and 100 healthy subjects enrolled for the study during a routine health survey (control group). Patients in the IDC group were stratified according to ejection fraction (EF). Those with EF values were higher than 35% were placed into subgroup 1; subgroup 2 included patients with an EF value of 15% - 35%; and subgroup 3 consisted of those whose EF values less than 15%. RESULTS: The frequency of HLA-DQA1 *0501 alleles was significantly higher in the IDC group (0.39) than that in the HF group (0.12) and the control group (0.09) (both P < 0.05). Further analysis of the three IDC subgroups showed a higher frequency of DQA1 *0501 among patients with lower EF values (both P < 0.05, compared with subgroups 1 and 2). The frequency of DQA1 *0201 was higher in the control group than that in the IDC group (P < 0.05). CONCLUSIONS: The HLA-DQA1 *0501 allele confers susceptibility to IDC, while the DQA1 *0201 allele confers protection against it, which indicates that genetic background involved in IDC and heart failure is different. HLA-DQA1 genes are involved in the regulation of specific immune responses by auto- or foreign anti-myocardium antibody.
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