ANALYSIS OF HLA-DRB1 ALLELES OF HYPERTROPHIC CARDIOMYOPATHY IN JAPANESE POPULATION
M.Sada, K.Otsu, M.Date, T.Kuzuya, M.Hori, T.Tsuji  Dept. of Surgical Research, National Cardiovascular Center, Osaka, Japan

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Hypertrophic cardiomyopathy (HCM) is a disorder of heart muscle characterized by idiopathic left ventricular hypertrophy. Clinical and genetic studies suggest that HCM may result from the interaction of the disease-causing mutations and environmental and/or other genetic factors. To define the contribution of an immune mechanism in the pathogenesis of HCM, we have analyzed the association of specific HLA-DRB1 alleles with HCM in Japan. HLA-DRB1 genotyping using polymerase chain reaction-sequence specific primers (PCR-SSP) and PCR-line probe assay (PCR-LiPA) methods was performed on 107 Japanese patients with HCM. Patients with HCM had a significantly increased frequency of possessing the DRB1*0406 allele compared to the normal healthy control (9.8% vs. 3.5%, p=.00013, RR=3.1). HCM is further classified into two hemodynamic subtypes: an obstructive form (HOCM) and a non-obstructive form (HNCM). The frequencies of the DRB1*1401 and DRB1*0405 in the HOCM(n=18) were significantly higher than in the HNCM(n=84) (p=.002, RR=6.5, and p=.006, RR=4.4). Apical HCM is a subtype of nonobstructive HCM characterized by a unique spade-like configuration to the hypertrophy and marked apical obliteration. The frequency of DRB1*1302 allele in apical HCM(n=28) and nonapical HCM(n=74) was 15.5% and 4.1%, respectively (p=.007, RR=4.5). The DRB1*0406 allele was present in 3.7% of the patients with familial HCM, while in the sporadic form of HCM, the DRB1*0406 was found in 22.6% of the patients (p=.026, RR=7.7). HOCM, apical HCM, and sporadic HCM were associated with increased frequencies of different DRB1 allele. HCM patients bearing the same causative mutation vary in the extend of left ventricular hypertrophy and degree of ventricular outflow tract observation, suggesting that the morphological heterogeneity may not be solely due to the disease-causing mutation. Susceptibility to HCM is, in part, controlled by HLA genes themselves or an unknown gene(s), the locus for which is closed to the DRB1 gene.