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oai:tokushima-u.repo.nii.ac.jp:02004196 2025-04-28T06:38:41Z 1713853213384:1713853295607

An independent validation study of three single nucleotide polymorphisms at the sex hormone-binding globulin locus for testosterone levels identified by genome-wide association studies 10363160 佐藤, 陽一 サトウ, ヨウイチ Sato, Youichi 佐藤 サトウ Sato 陽一 ヨウイチ Youichi 10396864 田嶋, 敦 タジマ, アツシ Tajima, Atsushi 田嶋 タジマ Tajima 敦 アツシ Atsushi カツラヤマ, モトキ カツラヤマ, モトキ Katsurayama, Motoki ノザワ, シアリ ノザワ, シアリ Nozawa, Shiari ヨシイケ, ミキ ヨシイケ, ミキ Yoshiike, Miki Koh, Eitetsue カナヤ, ジロウ カナヤ, ジロウ Kanaya, Jiro ナミキ, ミキオ ナミキ, ミキオ Namiki, Mikio マツミヤ, キヨミ マツミヤ, キヨミ Matsumiya, Kiyomi ツジムラ, アキラ ツジムラ, アキラ Tsujimura, Akira コマツ, キヨシ コマツ, キヨシ Komatsu, Kiyoshi イトウ, ナオキ イトウ, ナオキ Itoh, Naoki エグチ, ジロウ エグチ, ジロウ Eguchi, Jiro 30258610 井本, 逸勢 イモト, イッセイ Imoto, Issei 井本 イモト Imoto 逸勢 イッセイ Issei 30122253 山内, あい子 ヤマウチ, アイコ Yamauchi, Aiko 山内 ヤマウチ Yamauchi あい子 アイコ Aiko イワモト, テルアキ イワモト, テルアキ Iwamoto, Teruaki open access © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com independent validation study testosterone Japanese men single nucleotide polymorphism sex hormone-binding globulin genome-wide association studies STUDY QUESTION: Are the single nucleotide polymorphisms (SNPs) rs2075230, rs6259 and rs727428 at the sex hormone-binding globulin (SHBG) locus, which were identified by genome-wide association studies (GWASs) for testosterone levels, associated with testosterone levels in Japanese men? SUMMARY ANSWER: The SNP rs2075230, but not rs6259 and rs727428, is significantly associated with testosterone levels in Japanese men. WHAT IS ALREADY KNOWN: Previous GWASs have revealed that rs2075230 is associated with serum testosterone levels in 3495 Chinese men and rs6259 and rs727428 are associated with serum testosterone levels in 3225 men of European ancestry. STUDY DESIGN, SIZE, AND DURATION: This is an independent validation study of 1687 Japanese men (901 in Cohort 1 and 786 in Cohort 2). PARTICIPANTS/MATERIALS, SETTING AND METHOD: Cohort 1 (20.7 ± 1.7 years old, mean ± SD) and Cohort 2 (31.2 ± 4.8 years) included samples obtained from university students and partners of pregnant women, respectively. The three SNPs were genotyped using either TaqMan probes or restriction fragment length polymorphism PCR. Blood samples were drawn from the cubital vein of the study participants in the morning, and total testosterone and SHBG levels were measured using a time-resolved immunofluorometric assay. Association between each SNP and testosterone levels was evaluated by meta-analysis of the two Japanese male cohorts. MAIN RESULTS AND THE ROLE OF CHANCE: The age of the two cohorts was significantly different (P < 0.0001). We found that rs2075230 was significantly associated with serum testosterone levels (βSTD = 0.15, P = 7.2 × 10−6); however, rs6259 and rs727428 were not (βSTD = 0.17, P = 0.071; βSTD = 0.082, P = 0.017, respectively), after adjusting for multiple testing in a combined analysis of two Japanese male cohorts. Moreover, rs2075230, rs6259 and rs727428 were significantly associated with high SHBG levels (βSTD = 0.22, P = 3.4 × 10−12; βSTD = 0.23, P = 6.5 × 10−6 and βSTD = 0.21, P = 3.4 × 10−10, respectively). LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: This study had differences in the age and background parameters of participants compared to those observed in previous GWASs. In addition, the average age of participants in the two cohorts in our study also differed from one another. Therefore, the average testosterone levels, which decrease with age, between studies or the two cohorts were different. WIDER IMPLICATIONS OF THE FINDINGS: The three SNPs have a considerable effect on SHBG levels and hence may indirectly affect testosterone levels. STUDY FUNDING/COMPETING INTERESTS: This study was supported partly by the Ministry of Health and Welfare of Japan (1013201) (to T.I.), Grant-in-Aids for Scientific Research (C) (26462461) (to Y.S.) and (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.). There are no conflicts of interest to declare. Oxford University Press 2017-06-14 eng journal article VoR 323571 https://tokushima-u.repo.nii.ac.jp/records/2004196 https://doi.org/10.1093/hropen/hox002 10.1093/hropen/hox002 23993529 Human Reproduction Open 2017 1 hox002 https://tokushima-u.repo.nii.ac.jp/record/2004196/files/hropen_2017_1_hox002.pdf application/pdf 815 KB 2018-01-24 https://tokushima-u.repo.nii.ac.jp/record/2004196/files/hropen_2017_1_hox005.pdf application/pdf 59.5 KB 2018-01-24