Analysis of Genetic Factors in Multi-nodular Goiter

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: Takahiko Kogai 獨協医科大学, 医学部, 教授 (40711693)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: サイログロブリン遺伝子 / 多結節性甲状腺腫 / KEAP1

Outline of Final Research Achievements

Multinodular goiter (MNG) is observed in 1-4 % of the population, and genetic factors, in addition to environmental and endogenous endocrine factors, has been considered to contribute to its onset. We aimed to elucidate the genetic factors of MNG, and thus comprehensively searched for germline mutations in oncogenes related to thyroid nodule, as well as genes involved in thyroid hormone synthesis, using blood samples from 129 individuals. The results indicated that missense mutation(s) in thyroglobulin gene was found in ~75% of the cases. The tumor formation mechanism following the two-hit hypothesis, like hereditary tumors, was suggested in cases with germline mutation of KEAP1. Furthermore, the association of a novel microsatellite polymorphism in congenital hypothyroidism was also demonstrated in adult MNG.

Free Research Field

臨床検査

Academic Significance and Societal Importance of the Research Achievements

成人でしばしば認められる多結節性甲状腺腫の遺伝学的背景として、サイログロブリン遺伝子のミスセンスバリアントの頻度が高いことが確認された。また、悪性腫瘍のリスク因子として重要な遺伝性腫瘍症候群の原因遺伝子が、約10％程度の症例に関与していることが明らかとなった。サイログロブリン遺伝子のバリアント自体も悪性腫瘍との関連が報告されており、多結節性甲状腺腫の遺伝診療で、今後重要な情報となる悪性腫瘍合併リスクを推測するうえで、甲状腺腫関連遺伝子の網羅的検査が有用である可能性が示唆された。