title: Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese patients with cryptorchidism.
abstract: OBJECTIVE
  Although insulin-like factor 3 (INSL3) and its receptor leucine-rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor affecting testis descent (LGR8/GREAT) are essential for the gubernacular development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with cryptorchidism (CO), and there is no report documenting a positive association of CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development of CO.
  
  
  METHODS
  Sixty-two Japanese CO patients and 60 fertile males were studied. INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and LGR8/GREAT was examined by denaturing high-performance liquid chromatography followed by direct sequencing for exons with abnormal chromatogram patterns.
  
  
  RESULTS
  No definitive mutation was identified in both genes. Six polymorphisms were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr polymorphism in INSL3 was strongly associated with CO (p=0.0024, odds ratio=5.3, 95% confidence interval=1.7-17).
  
  
  CONCLUSIONS
  The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of CO.
authors.affiliation: Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yamazawa
authors.forename: Yuka
authors.initials: Y
authors.lastname: Wada
authors.forename: Isoji
authors.initials: I
authors.lastname: Sasagawa
authors.forename: Katsuya
authors.initials: K
authors.lastname: Aoki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ueoka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003456:Cryptorchidism / Q000235:genetics*; D006801:Humans; D007223:Infant; D007328:Insulin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; C472867:RXFP2 protein, human; D043562:Receptors, G-Protein-Coupled