Abstract
Purpose
A previous genome-wide association study in European men identified four single nucleotide polymorphism (SNP) loci associated with male infertility. Our aim was to replicate, if possible, the association of these SNPs with Japanese male infertility.
Methods
We genotyped four SNPs (rs5911500, rs10246939, rs2059807, and rs11204546) in 517 Japanese patients with male infertility and 369 fertile controls using SNP-specific real-time polymerase chain reaction TaqMan assays. Subsequently, we divided patients with male infertility into azoospermia (n = 417) and oligospermia subgroups (n = 70).
Results
The four SNPs previously identified in European men showed no significant association with collective male infertility in our Japanese cohort. However, allele frequency analysis did indicate a significantly higher frequency of the rs11204546 C allele of the OR2W3 gene in the oligospermia subset of infertility patients compared with controls (p = 0.0037; odds ratio = 1.74; 95 % confidence interval, 1.21–2.53).
Conclusions
Although this study was somewhat limited by overall sample size, the OR2W3 gene polymorphism rs11204546 was significantly associated with oligospermia in Japanese men, suggesting that OR2W3 might be involved in genetic susceptibility to Japanese male infertility as well as in European males.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Krausz C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab. 2011;25:271–85.
Navarro-Costa P, Goncalves J, Plancha CE. The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility. Hum Reprod Update. 2010;16:525–42.
Mfady DS, Sadiq MF, Khabour OF, Fararjeh AS, Abu-Awad A, Khader Y. Associations of variants in MTHFR and MTRR genes with male infertility in the Jordanian population. Gene. 2014;536:40–4.
Gupta N, Sarkar S, David A, Gangwar PK, Gupta R, Khanna G, et al. Significant impact of the MTHFR polymorphisms and haplotypes on male infertility risk. PLoS One. 2013;8:e69180.
Gupta N, Gupta S, Dama M, David A, Khanna G, Khanna A, et al. Strong association of 677 C > T substitution in the MTHFR gene with male infertility–a study on an indian population and a meta-analysis. PLoS One. 2011;6:e22277.
Norambuena PA, Diblik J, Krenkova P, Paulasova P, Macek M, Macek Sr M. An ADP-ribosyltransferase 3 (ART3) variant is associated with reduced sperm counts in Czech males: case/control association study replicating results from the Japanese population. Neurol Endocrinol Lett. 2012;33:48–52.
Okada H, Tajima A, Shichiri K, Tanaka A, Tanaka K, Inoue I. Genome-wide expression of azoospermia testes demonstrates a specific profile and implicates ART3 in genetic susceptibility. PLoS Genet. 2008;4:e26.
Fang J, Wang S, Wang H, Zhang S, Su S, Song Z, et al. The Cytochrome P4501A1 gene polymorphisms and idiopathic male infertility risk: a meta-analysis. Gene. 2014;535:93–6.
Aston KI, Carrell DT. Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. J Androl. 2009;30:711–25.
Hu Z, Xia Y, Guo X, Dai J, Li H, Hu H, et al. A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia. Nat Genet. 2012;44:183–6.
Sato Y, Jinam T, Iwamoto T, Yamauchi A, Imoto I, Inoue I, et al. Replication study and meta-analysis of human nonobstructive azoospermia in Japanese populations. Biol Reprod. 2013;88:87.
Aston KI, Krausz C, Laface I, Ruiz-Castane E, Carrell DT. Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent. Hum Reprod. 2010;25:1383–97.
Yoshida K, Yoshihara K, Adachi S, Haino K, Nishino K, Yamaguchi M, et al. Possible involvement of the E-cadherin gene in genetic susceptibility to endometriosis. Hum Reprod. 2012;27:1685–9.
Zhang Y, He XJ, Song B, Ye L, Xie XS, Ruan J, Zhou FS, Zuo XB, Cao YX, Du WD. Association of single nucleotide polymorphisms in the USF1, GTF2A1L and OR2W3 genes with non-obstructive azoospermia in the Chinese population. J Assist Reprod Genet. 2014.
Flegel C, Manteniotis S, Osthold S, Hatt H, Gisselmann G. Expression profile of ectopic olfactory receptors determined by deep sequencing. PLoS One. 2013;8:e55368.
Acknowledgments
We thank the DNA donors and our supporting medical staff for making this study possible. We are grateful to C. Seki and A. Yukawa for their technical assistance.
Disclosure
The authors declare no potential conflicts of interest exist with respect to the research, authorship, and/or publication of this article.
Author information
Authors and Affiliations
Corresponding author
Additional information
Capsule OR2W3 might be involved in genetic susceptibility to Japanese male infertility.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary Table 1
(XLS 21 kb)
Rights and permissions
About this article
Cite this article
Chihara, M., Yoshihara, K., Ishiguro, T. et al. Susceptibility to male infertility: replication study in Japanese men looking for an association with four GWAS-derived loci identified in European men. J Assist Reprod Genet 32, 903–908 (2015). https://doi.org/10.1007/s10815-015-0468-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-015-0468-4