講演情報

[BP-2]腎性低尿酸血症の原因遺伝子URAT1/SLC22A12の日本人30,685名における臨床遺伝学的解析：実際的診断に向けて

^○河村優輔¹, 中山昌喜¹, 清水聖子¹, 豊田優¹, 染谷真澄¹, 小田悠太¹, 鳥羽美帆¹, 川口真¹, 鈴木聡子², 岩澤聡子², 中島宏², 高田龍平³, 角田正史², 有澤幸吉⁴, 嶽崎俊郎⁵, 田中恵太郎⁶, 市田公美⁷, 若井建志⁸, 四ノ宮成祥¹, 松尾洋孝¹ (1.防衛医科大学校分子生体制御学講座, 2.防衛医科大学校衛生学公衆衛生学講座, 3.東京大学医学部附属病院薬剤部, 4.徳島大学大学院医歯薬学研究部医科学部門社会医学系予防医学, 5.鹿児島大学大学院医歯学総合研究科国際離島医療学, 6.佐賀大学医学部社会医学講座予防医学, 7.東京薬科大学病態生理学教室, 8.名古屋大学大学院医学系研究科予防医学)

※12月15日（木）と16日（金）で同一演題の発表を行います。

Renal hypouricemia (RHUC) is an inherited disorder caused by nonfunctional variants of URAT1/SLC22A12, which encodes a urate reabsorption transporter. W258X (rs121907892) and R90H (rs121907896) are known to be the two commonest nonfunctional variants of URAT1 (NFV-URAT1) for Japanese patients with RHUC. RHUC is relatively frequent in Japanese, but no studies have been reported for the distribution of NFV-URAT1 in hypouricemic individuals (serum uric acid, SUA ≦ 3.0 mg/dl; normal range: 3.0～7.0 mg/dl) in a large population. Our investigation for 30,685 Japanese demonstrated that 0.97% of males and 6.94% of females were hypouricemic individuals. With 1,040 hypouricemic individuals whose DNA were available, we genotyped NFV-URAT1 and revealed that 85.7% (male) and 73.7% (female) in hypouricemia (SUA ≦ 2.0 mg/dl) were suspected as RHUC due to having at least one allele of NFV-URAT1. Furthermore, the effects of NFV-URAT1 on SUA and fractional excretion of uric acid (FE_UA; normal range: 5.5～11.1%), the characteristic clinical parameters of RHUC, were evaluated in 2,240 individuals whose urinary data were available. As a result, NFV-URAT1 alleles significantly increased FE_UA and decreased SUA in both sexes. Especially, FE_UA was increased up to 45% and SUA was decreased to less than 1.0 mg/dl in those with two alleles. Together with previous reports, we herein propose more practical diagnosis of RHUC based on the specific distribution patterns of FE_UA and SUA data, which leads to predict the number of nonfunctional variants of causative genes for RHUC even before genetic tests.

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