Susceptibility gene for non-obstructive azoospermia located near HLA-DR and -DQ loci in the HLA class II region

Hum Genet. 2002 Feb;110(2):192-7. doi: 10.1007/s00439-001-0657-3. Epub 2002 Jan 22.


The technical developments and expanded indications for testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) provide great advantages for patients with non-obstructive azoospermia. Such success, however, also means that genetic abnormalities in non-obstructive azoospermia can be transmitted to the next generation, demonstrating the importance of being able to understand the genetic background of non-obstructive azoospermia. We have previously reported that human leukocyte antigens (HLA)-A33 and -B44 in the HLA class I region and the HLA-DRB1*1302 allele in the HLA class II region are linked to susceptibility to non-obstructive azoospermia in Japanese men. However, strong linkage of HLA-DRB1*1302 with HLA-A33 and -B44 is also evident in the Japanese population. Thus, uncertainty prevails as to whether the HLA class I or class II molecule is more directly associated with non-obstructive azoospermia. In the present study, we performed association analysis with 21 polymorphic microsatellite markers identified near the HLA genes to map the gene involved in the development of non-obstructive azoospermia more precisely. Microsatellite markers located in the HLA class I region or the class III region showed no statistically significant association with this disorder, although once again the HLA-A33 and -B44 alleles showed a significant association. In contrast, some of the microsatellite markers in the HLA class II region and at the HLA-DRB1 and -DQB1 loci displayed strong associations with non-obstructive azoospermia. Taken together, our previous and present data suggest that the critical region for development of non-obstructive azoospermia is near the HLA-DRB1 and -DQB1 segments in the HLA class II region.

MeSH terms

  • Asian Continental Ancestry Group
  • Biopsy
  • Chromosome Mapping
  • Expressed Sequence Tags
  • Genes, MHC Class II*
  • Genetic Markers
  • Genetic Predisposition to Disease / genetics*
  • HLA-DQ Antigens / genetics*
  • HLA-DR Antigens / genetics*
  • Humans
  • Japan
  • Male
  • Microsatellite Repeats
  • Oligospermia / genetics*
  • Oligospermia / immunology
  • Oligospermia / pathology
  • Testis / pathology


  • Genetic Markers
  • HLA-DQ Antigens
  • HLA-DR Antigens