Abstract
The prevalence of spermatogenic failure (SF) has gradually increased during the past few decades at least in several countries. Although multiple factors would be involved in this phenomenon, one important factor would be excessive estrogen effects via estrogen receptors (ERs). Thus, we performed haplotype analysis of ESR2 encoding ERβ in 125 Japanese SF patients and 119 age-matched control males, using single nucleotide polymorphisms (SNPs) 1–9 that are widely distributed on the ∼120-kb genomic sequence of ESR2. Consequently, a linkage disequilibrium (LD) block was detected in an ∼60-kb region encompassing SNPs 2–7 in both groups, and four major estimated haplotypes were identified within the LD block. Furthermore, the most prevalent ‘TGTAGA’ haplotype was found to be significantly associated with SF, with the P-value obtained by the Cochran–Armitage trend test (0.0029) being lower than that obtained by a 100 000-times permutation test (0.0038) to cope with the problem of multiple comparisons. The results, in conjunction with our previous data indicating lack of a susceptibility factor on ESR1 encoding ERα, imply that the specific ‘TGTAGA’ haplotype of ESR2 raises the susceptibility to the development of SF.
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Acknowledgements
We would like to thank Dr Kamitsuji at StaGen Co., Ltd. for his critical advice in the genetic statistical analyses. This study was supported in part by the Environment Research and Technology Development Fund (C-0905) of the Ministry of Environment, by the Grants for Research on Intractable Diseases (H22-098), Health Research on Children, Youth and Families (H21–005), and Research on Risk of Chemical Materials (H20-004) from the Ministry of Health, Labor and Welfare, by the Grants-in-Aid for Scientific Research (S) (22227002) from the Japan Society for the Promotion of Science (JSPS), and Grant-in-Aid for Scientific Research on Innovative Areas (22132004) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and by the Grant from National Center for Child Health and Development (20C-2).
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Ogata, T., Fukami, M., Yoshida, R. et al. Haplotype analysis of ESR2 in Japanese patients with spermatogenic failure. J Hum Genet 57, 449–452 (2012). https://doi.org/10.1038/jhg.2012.53
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DOI: https://doi.org/10.1038/jhg.2012.53
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