title: Susceptibility gene for non-obstructive azoospermia located near HLA-DR and -DQ loci in the HLA class II region.
abstract: 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.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sada
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Miura
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Matsumiya
authors.forename: Rieko
authors.initials: R
authors.lastname: Gotoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakatani
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuyama
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
mesh_terms: D044466:Asian People; D001706:Biopsy; D002874:Chromosome Mapping; D020224:Expressed Sequence Tags; D005802:Genes, MHC Class II; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D018895:Microsatellite Repeats; D009845:Oligospermia / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D013737:Testis / Q000473:pathology
chemical_list: D005819:Genetic Markers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens