DNA Typing of HLA Class II Genes in Japanese Patients with Rheumatic Heart Disease

To study further the association between HLA and rheumatic valvular disease, DNA typing HLA class II genes (DRB1, DQA1, DQB1, DPA1 and DPB1) was performed in 72 unrelated Japanese patients with predominant mitral stenosis and 525 unrelated Japanese healthy controls, based on the polymerase chain reaction in combination of dot-blot hybridization with sequence-specific oligonucleotide probes. As compared with controls, patients with mitral stenosis showed increased frequencies of DQA1*0104 (18.1%v7.2%; RR=2.82,P=0.002,Pc=0.03) and DQB1*05031 (13.9%v4.8%; RR=3.23,P=0.002,Pc=0.05). In contrast, no significant deviation in the frequencies of DRB1, DPA1 or DPB1 alleles was observed in the patients. These observations suggest that the susceptibility to mitral stenosis is in part controlled by a gene (or genes) in close linkage disequilibrium with HLA-DQA1*0104 and DQB1*05031, i.e. the susceptibility gene may be mapped within the HLA-DQ region.