The role of testicular mono-ADP-ribosylation in men with idiopathic infertility

• Project/Area Number: 23510242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: The University of Tokushima
• Principal Investigator: TAJIMA Atsushi 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (10396864)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 遺伝子相互作用解析 / 遺伝リスク / 男性不妊症

Research Abstract

ART3 (ADP-ribosyltransferase 3) have been identified as a susceptibility gene for non-obstructive azoospermia (NOA) in humans. The objective of this study was to reveal a molecular and genetic basis for further understanding of pathophysiological roles of testicular ART3 involved in male infertility. (1) A proteomic analysis indicated that ART3 directly interacted with various proteins, some of which were expressed in human testes, and involved in spermatogenesis. (2) Case-control genetic association studies in Japanese populations demonstrated three NOA susceptibility loci, one of which contained a family gene of the ART3-interacting proteins. Thought the proteomic and genetic analyses, we identified promising candidate genes which might have roles in ART3-dependent regulation of spermatogenesis in humans.

Research Products

• [Journal Article] Estrogen promotes Leydig cell engulfment by macrophages in male infertility. (2014)
  • Author(s): Yu W, Zheng H, Lin W, Tajima A, Zhang Y, Zhang X, Zhang H, Wu J, Han D, Rahman NA, Korach KS, Gao GF, Inoue I, Li X.
  • Journal Title: J Clin Invest Volume: in press Issue: 6 Pages: 2709-2721
  • DOI: 10.1172/jci59901
  • Peer Reviewed
• [Journal Article] Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia (2014)
  • Author(s): Nishi A, Numata S, Tajima A, Kinoshita M, Kikuchi K, Shimodera S, Tomotake M, Ohi K, Hashimoto R, Imoto I, Takeda M, Ohmori T
  • Journal Title: Schizophrenia Bulletin Volume: 40(5) Issue: 5 Pages: 1154-63
  • DOI: 10.1093/schbul/sbt154
  • Peer Reviewed / Open Access
• [Journal Article] A nonsynonymous variant of IL1A is associated with endometriosis in Japanese population. (2013)
  • Author(s): Hata Y, Nakaoka H, Yoshihara K, Adachi S, Haino K, Yamaguchi M, Nishikawa N, Kashima K, Yahata T, Tajima A, Watanabe A, Akira S, Hosomichi K, Inoue I, Tanaka K.
  • Journal Title: J Hum Genet. Volume: 58 Issue: 8 Pages: 517-520
  • DOI: 10.1038/jhg.2013.32
  • NAID: 10031195280
  • Peer Reviewed
• [Journal Article] Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics (2013)
  • Author(s): Kinoshita M, Numata S, Tajima A, Shimodera S, Imoto I, Ohmori T
  • Journal Title: Epigenetics Volume: 8(6) Issue: 6 Pages: 584-590
  • DOI: 10.4161/epi.24621
  • Peer Reviewed
• [Journal Article] Replication study and meta-analysis of human nonobstructive azoospermia in Japanese populations. (2013)
  • Author(s): Sato Y
  • Journal Title: Biol Reprod Volume: 88 Issue: 4 Pages: 87-87
  • DOI: 10.1095/biolreprod.112.106377
  • Peer Reviewed
• [Journal Article] DNA methylation signatures of peripheral leukocytes in schizophrenia (2013)
  • Author(s): Kinoshita M, Numata S, Tajima A, Shimodera S, Ono S, Imamura A, Iga JI, Watanabe S, Kikuchi K, Kubo H, Nakataki M, Sumitani S, Imoto I, Okazaki Y, Ohmori T
  • Journal Title: Neuromolecular Med Volume: 15(1) Issue: 1 Pages: 95-101
  • DOI: 10.1007/s12017-012-8198-6
  • Peer Reviewed
• [Journal Article] Meta-analysis of association studies between DISC1 missense variants and schizophrenia in Japanese population. (2012)
  • Author(s): Kinoshita M, et al
  • Journal Title: Schizophr Res, Volume: 141(2-3): Issue: 2-3 Pages: 271-273
  • DOI: 10.1016/j.schres.2012.07.020
  • Peer Reviewed
• [Journal Article] High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway (2012)
  • Author(s): Kosuke Yoshihara
  • Journal Title: Clinical Cancer Research Volume: 18 Issue: 5 Pages: 1374-1385
  • DOI: 10.1158/1078-0432.ccr-11-2725
  • Peer Reviewed
• [Journal Article] Hunting for genes for hypertension: the Millennium Genome Project for Hypertension. (2012)
  • Author(s): Tabara Y
  • Journal Title: Hypertens Res Volume: 35 Issue: 6 Pages: 567-573
  • DOI: 10.1038/hr.2012.41
  • Peer Reviewed
• [Journal Article] Autosomal and Y-chromosomal STR markers reveal a close relationship between Hokkaido Ainu and Ryukyu islanders (2012)
  • Author(s): K. Koganebuchi, T. Katsumura, S. Nakagome, H. Ishida, S. Kawamura, H. Oota
  • Journal Title: Anthropological Science Volume: 120 Issue: 3 Pages: 199-208
  • DOI: 10.1537/ase.120322
  • NAID: 10031145903
  • ISSN: 0918-7960, 1348-8570
  • Peer Reviewed
• [Journal Article] The history of human populations in the Japanese Archipelago inferred from genome-wide SNP data with a special reference to the Ainu and the Ryukyuan Populations. (2012)
  • Author(s): Jinam T, Nishida N, Hirai M, Kawamura S, Oota H, Umetsu K, Kimura R, Ohashi J, Tajima A, Yamamoto T, Tanabe H, Mano S, Suto Y, Kaname T, Naritomi K, Yanagi K, Niikawa N, Omoto K. Saitou N
  • Journal Title: Journal of Human Genetics Volume: 57巻 Issue: 12 Pages: 787-79
  • DOI: 10.1038/jhg.2012.114
  • NAID: 10031145887
  • Peer Reviewed
• [Journal Article] Identification of independent risk loci for Graves' disease within the MHC in the Japanese population. (2011)
  • Author(s): Nakabayashi K, Shirasawa S
  • Journal Title: J Hum Genet Volume: 56(11) Issue: 11 Pages: 772-778
  • DOI: 10.1038/jhg.2011.99
  • NAID: 10030661591
  • Peer Reviewed
• [Journal Article] A Systems Genetics Approach Provides a Bridge from Discovered Genetic Variants to Biological Pathways in Rheumatoid Arthritis (2011)
  • Author(s): Nakaoka Hirofumi; Cui Tailin; Tajima Atsushi, et al
  • Journal Title: PLOS ONE Volume: 6:9 Issue: 9 Pages: e25389-e25389
  • DOI: 10.1371/journal.pone.0025389
  • Peer Reviewed
• [Presentation] Genome-wide association study of plasma homocysteine and DNA methylation in patients with schizophrenia (2013)
  • Author(s): Kinoshita M, Numata S, Tajima A, Shimodera S, Imoto I, Ohmori T
  • Organizer: 11^<th> World Congress of Biological Psychiatry
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] Functional variants of the MTHFR gene and schizophrenia in the Japanese population (2013)
  • Author(s): Nishi A, Numata S, Tajima A, Kinoshita M, Shimodera S, Ohi K, Hashimoto R, Imoto I, Takeda M, Ohmori T
  • Organizer: Neuro 2013
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] Functional variants of the MTHFR gene and schizophrenia in the Japanese population. (2013)
  • Author(s): Nishi A, Numata S, Tajima A, Kinoshita M, Shimodera S, Ohi K, Hashimoto R, Imoto I, Takeda M, Ohmori T.
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都府）
• [Presentation] Plasma homocysteine and schizophrenia: a gender-specific meta-analysis. (2013)
  • Author(s): Numata S, Kikuchi K, Tajima A, Kinoshita M, Shimodera S, Tomotake M, Imoto I, Ohmori T.
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 国立京都国際会館（京都府）
• [Presentation] Genome-wide methylation status of human leukocytes in mood disorders. (2013)
  • Author(s): Numata S, Kinoshita M, Tajima A, Shimodera S, Iga J, Watanabe S, Imoto I, Ohmori T.
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 国立京都国際会館（京都府）
• [Presentation] Genome-wide association study of plasma homocysteine and DNA methylation in patients with schizophrenia. (2013)
  • Author(s): Kinoshita M, Numata S, Tajima A, Shimodera S, Imoto I, Ohmori T.
  • Organizer: 11th World Congress of Biological Psychiatry
  • Place of Presentation: 国立京都国際会館（京都府）
• [Presentation] HNF1B、JAZF1 多型の前立腺がん発症リスクに関するメタアナリシス (2012)
  • Author(s): 阿部夏季、菅恵梨、田嶋敦、井本逸勢
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] 多因子遺伝性疾患における遺伝的リスクの集団間差 : 東アジアにおける2 型糖尿病関連遺伝子多型を例として (2012)
  • Author(s): 渡邉美恵、田嶋敦、井本逸勢
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] 生殖補助医療技術が出生時のDNA メチル化状態に及ぼす影響の検討 (2012)
  • Author(s): 久須美真紀、中林一彦、前原佳代子、田嶋敦、副島英伸、吉原一、 秦健一郎
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] HNF1B、JAZF1多型の前立腺がん発症リスクに関するメタアナリシス (2012)
  • Author(s): 阿部夏季
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル（東京都）
• [Presentation] 多因子遺伝性疾患における遺伝的リスクの集団間差：東アジアにおける2型糖尿病関連遺伝子多型を例として (2012)
  • Author(s): 渡邉美恵
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル（東京都）
• [Presentation] 生殖補助医療技術が出生時のDNAメチル化状態に及ぼす影響の検討 (2012)
  • Author(s): 久須美真紀
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル（東京都）
• [Presentation] The history of human populations in the Japanese Archipelago inferred from genome-wide SNP data with a special reference to the Ainu and the Ryukyuan populations. (2012)
  • Author(s): Jinam T
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル（東京都）
• [Presentation] マイクロ RNA ネットワークの遺伝的多様性とヒト疾患との関わり (2011)
  • Author(s): 田嶋敦
  • Organizer: 日本人類遺伝学会第56回大会
  • Place of Presentation: 幕張メッセ(千葉県)
• [Presentation] 関節リウマチにおけるシステムズ・ジェネティクス・アプローチ?感受性遺伝子座から生物学的経路の推定 (2011)
  • Author(s): 中岡博史、崔泰林、田嶋敦、光永滋樹、猪子英俊、井ノ上逸朗
  • Organizer: 日本人類遺伝学会第56回大会
  • Place of Presentation: 幕張メッセ(千葉県)
• [Presentation] マイクロRNAネットワークの遺伝的多様性とヒト疾患との関わり (2011)
  • Author(s): 田嶋敦
  • Organizer: 日本人類遺伝学会第56回大会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] 関節リウマチにおけるシステムズ・ジェネティクス・アプローチ～感受性遺伝子座から生物学的経路の推定 (2011)
  • Author(s): 中岡博史
  • Organizer: 日本人類遺伝学会第56回大会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] 愛知がんセンター大規模病院疫学研究システムに基づくHLAクラスIIアレルとピロリ菌感染に関する横断研究 (2011)
  • Author(s): 田嶋敦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県)