Associations between body mass index and serum uric acid levels in a Japanese population were significantly modified by LRP2 rs2544390

The genome-wide association study identified associations between the LRP2 polymorphism rs2544390 and serum uric acid (SUA) levels in a Japanese population. Our previous study on the LRP2 rs2544390 polymorphism identified an interaction between SUA and alcohol consumption. Here, we investigated an interaction with body mass index (BMI) using the same dataset. Subjects were 3,742 health checkup examinees (2,544 males and 1,198 females) aged 35-69 years. Those with the SLC22A12 258WW genotype, SLC2A9 rs11722228 C allele, and ABCG2 126QQ genotype and 141Q allele were selected for analysis to remove the strong influences of these genetic traits. In males, the odds ratio of BMI ≥25.0 relative to BMI <18.5 for hyperuricemia (SUA ≥7 mg/dL and/or under medication for hyperuricemia) was 6.58 (95% confidence interval [CI], 0.84-51.32) for CC, 10.08 (2.38-42.83) for CT, and 2.53 (0.54-11.78) for TT. The interaction was 0.59 (p=0.029) from the model including BMI (<25.0 and ≥25.0), genotype (CC/CT and TT), and the multiplicative interaction term between BMI ≥25.0 and the TT genotype. In females, the odds ratio of BMI ≥25.0 relative to BMI <18.5 for high SUA (≥5 mg/dL and/or under medication for hyperuricemia) was 6.35 (95%CI, 1.68-24.08) for CC, 4.55 (1.85-11.18) for CT, and 5.93 (1.97-17.90) for TT. The interaction term was significant in the opposite direction for females (OR=2.75, p=0.011). The association between BMI and SUA was therefore modified by the LRP2 polymorphism in this Japanese population.