Elucidation of novel disease formation mechanism in glycolipid metabolism disorder with congenital hypogonadotropic hypogonadism.

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09613
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: Sato Naoko 東京大学, 医学部附属病院, 登録研究員 (10383069)
• Co-Investigator(Kenkyū-buntansha): 瀬尾 美鈴 京都産業大学, 総合生命科学部, 教授 (60211223)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 中枢性性腺機能低下症 / 糖脂質代謝異常

Outline of Final Research Achievements

FGF-FGFR1 genetic network (FFN)’s gene mutations account for 30% of the etiology of hypogonadotropic hypogonadism (HH). Recently, it was reported that HH with FGF ligand of FFN’s gene mutations was accompanied by glycolipid metabolism. Additionally, we identified a mutation of gene A in HH patients with diabetes mellitus. Thus, we performed a gene mutation analysis for the purpose of clarifying new disease establishment mechanism of HH and glycolipid metabolism in 50 HH and identified mutations in both gene A and KLB in HH with severe obesity and/or diabetes mellitus. The results suggest that both gene A and KLB play an essential role in glycolipid metabolism with reproduction.

Free Research Field

生殖内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究の研究により、糖・脂質代謝異常症を伴うHH の責任遺伝子が同定されたことにより、視床下部－下垂体－性腺軸において、糖・脂質代謝とGnRH 分泌調節機構に関与するメカニズムが解明される糸口となり、糖・脂質代謝異常症およびHH の新規疾患成立機序の発見に繋がると考えられる。さらに、社会的な意義として、HHと糖脂質代謝異常に関する遺伝子診断により、適切な時期に糖尿病、脂質異常症、肥満の治療が開始され、代謝疾患の悪化を防ぎ、患者のQOL を向上させることが可能となる。