Cardiovascular disease and HLA

Major histocompatibility complex in man, HLA, has statistical association with many diseases with unknown etiology including cardiovascular diseases. Takayasu disease shows a strong association with HLA-Bw52-Dw12 haplotype in Japanese population. Numano et al. clearly demonstrated that HLA-Bw52-Dw12 positive patients with Takayasu disease showed severer clinical manifestations including hypertension, aortic insufficiency, etc. Behcet disease has an association with HLA-Bw51 in all ethnic groups so far tested. The association of Bw51 was stronger with male than with female patients, and stronger with severer than mild patients. Buerger disease is associated with HLA-Bw52 in Japanese population. Decreased frequency of HLA-B12 was reported in both Caucasian and Japanese patients with Buerger disease. Malignant rheumatoid arthritis is reported to be associated with HLA-DR4 and decreased frequency of HLA-B12 was also reported. Kawasaki disease is associated with HLA-Bw54 and DYT. Rheumatic heart disease, especially mitral stenosis, has a strong association with HLA-B7, and this association of B7 is stronger with male than with female patients. Idiopathic cardiomyopathy is reported to have an association with HLA-B12. Genetic mechanisms underlying these associations include: pleiotropy, linkage disequilibrium, and epistasis. Biological mechanisms have not been understood yet; however, a receptor model, or immune response genes, or immune suppression genes model might explain some of these associations between cardiovascular diseases and HLA.