Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese patients with cryptorchidism.

Abstract

BACKGROUND/AIMS:

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).

CONCLUSION:

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: Kazuki Yamazawa, Yuka Wada, Isoji Sasagawa, Katsuya Aoki, Katsuhiko Ueoka, Tsutomu Ogata
• Journal: Hormone research (Horm Res) Vol. 67 Issue 2 Pg. 73-6 ( 2007) ISSN: 0301-0163 [Print] Switzerland
• PMID: 17028442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2007 S. Karger AG, Basel.

Chemical References

• Insulin
• Leydig insulin-like protein
• Proteins
• RXFP2 protein, human
• Receptors, G-Protein-Coupled

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Cryptorchidism (genetics)
• Humans
• Infant
• Insulin (genetics)
• Male
• Middle Aged
• Mutation
• Polymorphism, Genetic
• Proteins (genetics)
• Receptors, G-Protein-Coupled (genetics)