• PMID: 25908655
• Gene Name: PSAT1
• Condition: Male infertility
• Association: Not associated
• Mutation: rs7867029, rs7174015, rs12870438 and rs724078
• Population size: 917
• Population details: 917 (791 fertile men, 76 patients with azoospermia, 50 patients with oligozoospermia)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: PSAT, USP8, EPSTI1, MAS1L, UBD
• Other associated phenotypes: Male infertility

Lack of replication of four candidate SNPs implicated in human male fertility traits: a large-scale population-based study

Sato Y, Tajima A, Tsunematsu K, Nozawa S, Yoshiike M, Koh E, Kanaya J, Namiki M, Matsumiya K, Tsujimura A, Komatsu K, Itoh N, Eguchi J, Imoto I, Yamauchi A, Iwamoto T.

STUDY QUESTION: Are the four candidate loci (rs7867029, rs12870438, rs7174015 and rs724078) for human male fertility traits, identified in a genome-wide association study (GWAS) of a Hutterite population in the USA, associated with semen quality traits in a Japanese population? SUMMARY ANSWER: The four single nucleotide polymorphisms (SNPs) rs7867029, rs12870438, rs7174015 and rs724078 have no association with semen parameters in a meta-analysis of two Japanese male cohorts. WHAT IS KNOWN ALREADY: Four (rs7867029, rs12870438, rs7174015 and rs724078) of the SNPs associated with family size or birth rate in the GWAS of a Hutterite population in the USA were associated with semen parameters in ethnically diverse men from Chicago, USA. STUDY DESIGN, SIZE, DURATION: This is a replication study in a total of 2015 Japanese subjects, including 791 fertile men and 1224 young men from the general population. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a replication study in two cohorts to assess whether the SNPs rs7867029, rs12870438, rs7174015 and rs724078 are associated with sperm concentration, semen volume, total sperm numbers, total motile sperm numbers or sperm motility. The rs12870438 SNP was detected by restriction fragment length polymorphism PCR while rs7174015, rs724078 and rs7867029 SNPs were genotyped using TaqMan probes. MAIN RESULTS AND THE ROLE OF CHANCE: This study indicated that none of the four SNPs rs7867029, rs12870438, rs7174015 and rs724078 displayed a significant association with semen parameters in the meta-analysis of two Japanese male cohorts. LIMITATIONS, REASONS FOR CAUTION: Only four SNPs identified in the Hutterite GWAS were examined for associations with semen quality traits in a Japanese population. In addition, the linkage disequilibrium structures around the testing markers were different between ethnic groups. WIDER IMPLICATIONS OF THE FINDINGS: Locus mapping studies using a set of tagging SNPs across the loci will be necessary in populations with larger sample sizes in order to understand the contribution of specific genes to semen quality. STUDY FUNDING/COMPETING INTEREST S: This study was supported in part by the Ministry of Health and Welfare of Japan (1013201) (to T.I.), Grant-in-Aids for Scientific Research (C) (23510242) (to A.Ta.) from the Japan Society for the Promotion of Science, the European Union (BMH4-CT96-0314) (to T.I.), and the Takeda Science Foundation (to A.Ta.). None of the authors has any competing interests to declare. CI - © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Sato, Youichi AU - Sato Y AD - Department of Pharmaceutical Information Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8505, Japan youichi.sato@tokushima-u.ac.jp atajima@med.kanazawa-u.ac.jp. FAU - Tajima, Atsushi AU - Tajima A AD - Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8503, Japan Department of Bioinformatics and Genomics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, 920-8640, Japan youichi.sato@tokushima-u.ac.jp atajima@med.kanazawa-u.ac.jp. FAU - Tsunematsu, Kouki AU - Tsunematsu K AD - Department of Pharmaceutical Information Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8505, Japan. FAU - Nozawa, Shiari AU - Nozawa S AD - Department of Urology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan. FAU - Yoshiike, Miki AU - Yoshiike M AD - Department of Urology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan. FAU - Koh, Eitetsue AU - Koh E AD - Department of Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8641, Japan. FAU - Kanaya, Jiro AU - Kanaya J AD - Department of Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8641, Japan. FAU - Namiki, Mikio AU - Namiki M AD - Department of Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8641, Japan. FAU - Matsumiya, Kiyomi AU - Matsumiya K AD - Department of Urology, Osaka Police Hospital, Osaka, 543-0035, Japan. FAU - Tsujimura, Akira AU - Tsujimura A AD - Department of Urology, Graduate School of Medicine, Faculty of Medicine, Osaka University, Osaka, 565-0871, Japan. FAU - Komatsu, Kiyoshi AU - Komatsu K AD - Department of Urology, Harasanshinkai Hospital, Fukuoka, 812-0033, Japan. FAU - Itoh, Naoki AU - Itoh N AD - Department of Urology, Sapporo Medical University, Sapporo, 060-8543, Japan. FAU - Eguchi, Jiro AU - Eguchi J AD - Department of Urology, Nagasaki University, Nagasaki, 852-8523, Japan. FAU - Imoto, Issei AU - Imoto I AD - Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8503, Japan. FAU - Yamauchi, Aiko AU - Yamauchi A AD - Department of Pharmaceutical Information Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8505, Japan.