Development of a disease risk estimation model with genetic and environmental factors for uric acid level.

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08682
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Kansai Medical University (2018-2020); Tohoku University (2017)
• Principal Investigator: MISAWA Kazuharu 関西医科大学, 医学部, 講師 (10525885)
• Co-Investigator(Kenkyū-buntansha): 三島 英換 東北大学, 大学病院, 助教 (00706939) ; 大内 基司 獨協医科大学, 医学部, 准教授 (20409155)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 尿酸値 / 痛風 / 遺伝率 / 稀な変異 / アフリカツメガエル / HEK293T

Outline of Final Research Achievements

Gout is a common arthritis caused by monosodium urate crystals. The heritability of serum urate levels is estimated to be 30% - 70%; however, common genetic variants account for only 7.9% of the variance in serum urate levels. This discrepancy is an example of missing heritability. The missing heritability suggests that variants associated with uric acid levels are yet to be found. By using genomic sequences of the ToMMo cohort, we identified rare variants of the SLC22A12 gene which encodes a urate transporter called URAT1. We identified new variants and carried out experiments to examine whether they affect the resulting protein variants. We grouped the participants with variants affecting urate uptake by URAT1 and analyzed the variance of serum urate levels. The results showed that the heritability explained by the SLC22A12 variants of men and women exceeds 10%, suggesting that rare variants underlie a substantial portion of the missing heritability of serum

Free Research Field

人類遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究課題の成果により、全ゲノム解析で見つかる稀な変異群が、血清尿酸値の「失われた遺伝率」のかなりの部分の根底にあることが分かりました。今後は、ゲノム上の稀な変異を検出することにより、尿酸値異常によって引き起こされる高尿酸血症や痛風などの病気にかかりやすい人を特定できるようになることが期待されています。
本研究成果は、米国遺伝学会誌「Genetics」2020年4月号に掲載されました。また2020年5月20日の朝日新聞にて記事にされました。