HLA-DR antigen and HLA-DRB1 genotyping with nonobstructive azoospermia in Japan

We previously reported that the HLA-A33, -B13, and -B44 antigens, which are major histocompatibility complex class I molecules, are involved in the su sceptibility of nonobstructive azoospermia in Japanese men. In this report, HLA-DR antigens, which are class II molecules, are investigated by advance d DNA typing in addition to classical serological typing to study a more co mplex genotype of HLA-DRB2. Genotyping was performed by the polymerase chai n reaction-sequence-specific primer (PCR-SSP) method of analysis and/or by a commercial rapid assay based on the polymerase chain reaction (PCR), foll owed by reverse dot-blot hybridization of PCR products (the Inno-LiPA assay ). The allele frequencies of the HLA-DR13 antigen and the -DRB1*1302 allele were significantly higher in Japanese subjects with nonobstructive azoospe rmia compared with a control group of healthy Japanese men, and these allel es were associated with relative risks for nonobstructive azoospermia of 4. 2 and 4.9, respectively. If we suppose this strong linkage to both HLA clas s I and II antigens is due to linkage disequilibrium, it may suggest the ex istence of a novel gene involved in spermatogenesis in the class III region , which is located between the class I and class II regions and contains se veral genes other than HLA.