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Genetic Polymorphisms of 17β-Hydroxysteroid Dehydrogenase 3 and the Risk of Hypospadias

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Title: Genetic Polymorphisms of 17β-Hydroxysteroid Dehydrogenase 3 and the Risk of Hypospadias
Authors: Sata, Fumihiro Browse this author
Kurahashi, Norie Browse this author
Ban, Susumu Browse this author
Moriya, Kimihiko Browse this author
Tanaka, Kazuyuki D. Browse this author
Ishizuka, Mayumi Browse this author
Nakao, Hiroyuki Browse this author
Yahata, Yuichiro Browse this author
Imai, Hirohisa Browse this author
Kakizaki, Hidehiro Browse this author
Nonomura, Katsuya Browse this author →KAKEN DB
Kishi, Reiko Browse this author →KAKEN DB
Keywords: Hypospadias
17β-Hydroxysteroid Dehydrogenase
Development of the Penis
Issue Date: 1-Aug-2010
Publisher: Elsevier
Journal Title: The Journal of Sexual Medicine
Volume: 7
Issue: 8
Start Page: 2729
End Page: 2738
Publisher DOI: 10.1111/j.1743-6109.2009.01641.x
Abstract: Introduction: Hypospadias is a common congenital anomaly caused by incomplete fusion of urethral folds. Development of the urethra and external genital system in the male fetus is an androgen-dependent process. In this regard, enzymes 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3, encoded by HSD17B3) and steroid 5α-reductase type 2 (encoded by SRD5A2) play crucial roles. Aim; To investigate the possible associations between common polymorphisms in HSD17B3 as well as well-known V89L polymorphism in SRD5A2 and risk of hypospadias. Methods: A case-control study was performed between 1999 and 2005. There were 89 Japanese boys with hypospadias and 291 newborn controls. We genotyped HSD17B3−1999T>C, +10A>G, +20A>G, +139G>A (V31I), +913G>A (G289S), and SRD5A2+336G>C (V89L) polymorphisms by allelic discrimination assay. We measured mRNA expression of the wildtype G289 allele and the mutant S289 allele of the HSD17B3 gene in the transfected human fetal kidney HEK293 cells. Main Outcome Measures: Assessment of hypospadias including its severity and HSD17B3 and SRD5A2 genes using DNA blood samples: allele and genotype distribution of single nucleotide polymorphisms in these two genes in cases and controls. Results: In our study, the risk of hypospadias was significantly higher in subjects carrying homozygous HSD17B3+913A (289S) alleles (odds ratio [OR]: 3.06; 95% confidence interval [CI]: 1.38–6.76). The risk of severe hypospadias was much higher in these subjects (OR: 3.93; 95% CI: 1.34–11.49). The mRNA expression levels of HSD17B3 G289 were higher than those of HSD17B3 S289 mutant (P < 0.001). In addition, the risk of severe hypospadias increased in boys carrying the SRD5A2+336C (89L) allele (OR: 3.19; 95% CI: 1.09–9.36). Conclusions: These results suggest that the HSD17B3 G289S polymorphism may be a potential risk modifier for hypospadias. Our findings provide evidence that a certain genotype related to androgen production may potentiate risk of hypospadias. Sata F, Kurahashi N, Ban S, Moriya K, Tanaka KD, Ishizuka M, Nakao H, Yahata Y, Imai H, Kakizaki H, Nonomura K, and Kishi R. Genetic polymorphisms of 17β-hydroxysteroid dehydrogenase 3 and the risk of hypospadias.
Rights: © 2010, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:環境健康科学研究教育センター (Center for Environmental and Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 岸 玲子

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