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

Abstract A genome-wide association study identified that LRP2rs2544390 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 LRP2polymorphism (rs3755166 G/A) in the promoter. Subjects were 5016 health checkup examinees (3409 males and 1607 females) aged 35 to 69 years with creatinine SLC22A12258WW , SLC2A9rs11722228C allele, ABCG2126QQ 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 ≥ 5/week relative to no drinking for hyperuricemia(SUA ≥ 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 ≥ 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 LRP2genotype and alcohol drinkingfor SUA. Since the low density lipoprotein-related protein 2 (megalin) encoded by LRP2is 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.