Significant interaction between LRP2 rs2544390 in intron 1 and alcohol drinking for serum uric acid levels among a Japanese population

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• 作者：Nobuyuki Hamajima^a ; ^{nhamajim@med.nagoya-u.ac.jp} ; Mariko Naito^a ; Rieko Okada^a ; Sayo Kawai^a ; Guang Yin^a ; Emi Morita^a ; Takahiro Higashibata^a ; Takashi Tamura^a ; Hiroko Nakagawa^a ; Hirotaka Matsuo^b ; Atsuyoshi Mori^c ; Kenji Wakai^a
• 关键词：ABCG2 ; ATP-binding cassette subfamily G member 2 ; ANOVA ; analysis of variance ; BMI ; body mass index ; bp ; base pairs ; CI ; confidence interval ; GLUT9 ; glucose transporter 9 ; GWAS ; genome-wide association study ; LDLR ; low-density lipoprotein receptor ; LRP2
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：15 July, 2012
• 卷：503
• 期：1
• 页码：131-136
• 文件大小：233 K

摘要

A genome-wide association study identified that LRP2 rs2544390 in intron 1 was associated with serum uric acid (SUA) levels among Japanese, as well as polymorphisms of SLC22A12, ABCG2, and SLC2A9. This study aimed to confirm the association of rs2544390 C/T with SUA, as well as another LRP2 polymorphism (rs3755166 G/A) in the promoter. Subjects were 5016 health checkup examinees (3409 males and 1607 females) aged 35 to 69 years with creatinine < 2.0 mg/dL. The subjects with SLC22A12 258WW, SLC2A9 rs11722228C allele, ABCG2 126QQ and 141Q allele (2546 males and 1199 females) were selected for analysis. Mean SUA was 6.03 mg/dL for CC, 6.18 mg/dL for CT, and 6.19 mg/dL for TT among males (p = 0.012), and 4.49 mg/dL, 4.45 mg/dL, and 4.42 mg/dL among females (not significant), respectively. No association was observed for rs3755166. The association with rs2544390 was stronger among male drinkers. The odds ratio of drinking 鈮?#xA0;5/week relative to no drinking for hyperuricemia (SUA 鈮?#xA0;7 mg/dL and/or under medication for hyperuricemia) was 1.11 (95%confidence interval, 0.67-1.84) among CC males, 1.75 (1.22-2.51) among CT males, and 3.13 (1.80-5.43) among TT males. The interaction terms with drinking 鈮?#xA0;5/week were 1.56 (p = 0.156) for CT and 2.87 (p = 0.005) for TT. This was the first report on the interaction between LRP2 genotype and alcohol drinking for SUA. Since the low density lipoprotein-related protein 2 (megalin) encoded by LRP2 is a multi-ligand endocytic receptor expressed in many tissues including the kidney proximal tubules, the association/interaction remained to be confirmed both epidemiologically and biologically.