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The frequencies of mutations in the beta-subunit of LH in fertile and infertile patients in Japan

Research Project

Project/Area Number 07671835
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOsaka Medical College

Principal Investigator

OKUDA Kiyoji  Osaka Medical College, 医学部, 講師 (90131325)

Co-Investigator(Kenkyū-buntansha) YAMADA Takashi  Osaka Medical College, 医学部, 専攻医 (10182536)
IMOTO Hirosumi  Osaka Medical College, 医学部, 専攻医 (30268205)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
KeywordsLH beta subunit / mutation / variant LH / RFLP / bioassay / frequency / PCR / 変異LH LH-β遺伝子 / 免疫学的測定法 / 多嚢胞性卵巣症候群 / 進化 / LH-β遺伝子 / 免疫学的測定 / 不妊症 / LH / 排卵障害 / 測定法
Research Abstract

A variant LH with 2 mutalions in the LHbeta gene was reported, which was undetectable using specific monoclonal antibbdies. To evaluate the clinical significance of the anomalous LH variant, we analyzed the prevalence of the mutant of the LHbeta-subunit in Japan. One hundred and six infertile female patients (group I), of whom 50 have ovulatory cycles (group Ia) and 56 have ovulatory disturbances (group Ib), 113 patients with multiple normal courses of pregnancy (group II), and 119 randomly selected males patients who consulted our hospital (group III) were studied. DNA was extracted from peripheral blood leukocytes and restriction fragment length polymorphism (RFLP) analysis was carried out to screen for mutations of the LHbeta gene amplified by PCR.The serum concentrations of LH were measured by in an vitro bioassay (LH-Bio) and immunoassay using SPAC (LH-SPAC) and IMX (LH-IMX) kits. There were no significant differences in the frequencies of homozygote and heterozygotes for the mutant LHbeta gene among the 3 groups (0.9% and 10.4% in group I, 0.9% and 8.8% in group II and 1.7% and 8.4% in group III, respectively). The frequency of heterozygosity was identical between group Ia (10.0%) and group Ib (10.7%). The biological activity of LH in the patients with variant LH was higher than it in patients with wild LH, however, a common phenotype due to these mutations has not been detected so far in 4 homozygous patients or 31 heterozygous patients. The ratios of LH-SPAC/LH-IMX were classified into 3 groups according to the genotypes of the LHbeta gene. This mutant is in 8.4%-10.4% of the Japanese population, but it does not have a great influence upon ovulation and reproductive function. However, we must keep in mind the presence of this anomalous LH when estimating the LH value and further study is needed on the role of anomalous LH in reproductive function.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 奥田喜代司: "ゴナドトロビンの遺伝子解析とその臨床"" 産婦人科の世界. 46巻、8号. 575-582 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyoji Okuda,: "Antigenic alteration of anomalous human luteinizing hormone caused by two chorionic gonadotropin-type substitions"" Biochemical and Biophysical Research Communications. 200. 584-590 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyoji Okuda,: "“Hereditary abnormality of luteinizing hormone resulting in Discrepant serum concentrations determined by different assays"" Endocrine Journal. 41(6). 639-644 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 奥田喜代司: "ゴナドトロビン単独欠損症" 内科 第75巻. 6号. 1629 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 井本広済: "排卵障害例における変異LHの頻度"" 産婦人科の進歩. 47巻6号. 827-831 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 井本広済: "多嚢胞卵巣症候群における変異LHの意義" 産婦人科の進歩. 50巻2号. 217-219 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyoji Okuda, Takashi Yamada, Hirosumi Imoto, Hideyuki Komatubara, and Osamu Sugimoto: "Antigenic alteration of anomalous human luteinizing hormone caused by two chorionic gonadotropin-type substitions"" Biochemical and Biophysical Research Communications. 200. 584-590 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyoji Okuda, Junta Takamatsu, Tadashi Okazaki, Takashi Yamada, Michio Saeki, and Osamu Sugimoto: "Hereditary abnormality of luteinizing hormone resulting in Discrepant serum concentrations determined by different assays"" Endocrine Journal. 41(6). 639-644 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 奥田喜代司, ら: "Antigenic alteration of an anomalous human luteinizing hormone,caused by two chorionic gonadotropin-type aminoacid substitutions" Biophys.Biochem.Res.Comm. 200(1). 584-590 (1994)

    • Related Report
      1997 Annual Research Report
  • [Publications] 奥田喜代司, ら: "Hereditary Abnormality of Luteinizing Hormone Resulting in Diserepant Serum Concentrations Determined by Different Assay." Endocrine Journal. 41(6). 639-644 (1994)

    • Related Report
      1997 Annual Research Report
  • [Publications] 奥田喜代司, ら: "ゴナドトロピンの遺伝子解析とその臨床" 産婦人科の世界. 46(8). 575-582 (1994)

    • Related Report
      1997 Annual Research Report
  • [Publications] 井本広済, ら: "排卵障害例における変異LHの頻度" 産婦人科の進歩. 47. 827-837 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 奥田喜代司: "ゴナドトロピン単独欠損症" 内科. 75(6). 1629 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 井本広済, ら: "多嚢胞卵巣症候群における変異LHの意義" 産婦人科の進歩. 50. 217-219 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 奥田喜代司ら: "Antigenic alteration of an anomalous human luteinizing hormone causedby two chorionic gonadotropin-type amino-acid substitutions" Biophys. Biochem. Res. Comm.200(1). 584-590 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] 奥田喜代司ら: "Hereditary Abnormality of Luteinizing Hormone Resulting in Discrepant Serum Concentrations Determined by Different Assay" Endocrine Journal. 41(6). 639-644 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] 奥田喜代司ら: "ゴナドトロピンの遺伝子解析とその臨床" 産婦人科の世界. 46(8). 574-582 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] 井本広済ら: "排卵障害例における異変LHの頻度" 産婦人科の進歩. 47. 827-837 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 奥田喜代司: "ゴナドトロピン単独欠損症" 内科. 75(6). 1629 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 奥田 喜代司: "ゴナドトロピン単独欠損症" 内科. 75. 1629-1629 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 井本 広済: "排卵障害例における変異LHの頻度" 産婦人科の進歩. 47. 827-831 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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