1132: Interaction of LOC100507053, ADH1B, and ADH1C with Alcohol Consumption for Elevated Serum Urate Levels and Gout in People of European Ethnicity

Min Hui Chuah¹, Ruth Topless², Gregory Gamble¹, Nicholas Sumpter³, Lisa Stamp⁴, Tony Merriman² and Nicola Dalbeth¹, ¹University of Auckland, Auckland, New Zealand, ²University of Otago, Dunedin, New Zealand, ³University of Alabama at Birmingham, Birmingham, AL, ⁴University of Otago, Christchurch, New Zealand

Background/Purpose: Alcohol consumption is a risk factor for hyperuricaemia and gout. Multiple single nucleotide polymorphisms (SNPs) have been identified as associated with both habitual alcohol consumption and serum urate levels or gout in separate genome-wide association studies (GWASs). The aim of this study was to systematically identify and characterize interactions between these shared SNPs and alcohol consumption for association with hyperuricaemia and gout.

Methods: This research was conducted using cross-sectional data from the UK Biobank. The association of alcohol consumption (units per week) with serum urate levels and gout was tested among more than 340,000 individuals of European ethnicity. Candidate SNPs for interaction analysis were identified by comparing serum urate, gout, and alcohol consumption GWASs for overlap and selecting the lead shared urate or gout-associated SNP at each locus. Multivariable-adjusted linear and logistic regression analyses were conducted with the inclusion of an interaction term to identify SNP-alcohol consumption interactions for hyperuricaemia and gout. The nature of these interactions was characterized using genotype-stratified association analysis.

Results: Alcohol consumption was associated with elevated serum urate levels (β 0.49, SE 0.01, P < 1.0 x 10^-300) and gout (OR 1.013, 95% CI 1.013-1.014, P = 1.2 x 10^-173). For hyperuricaemia, interactions were identified between alcohol consumption and LOC100507053 rs11733695 (P = 1.4 x 10^-3), ADH1B rs1229984 (P = 7.9 x 10^-13), and ADH1C rs141973904 (P = 5.1 x 10^-6). ADH1B rs1229984 additionally demonstrated interaction with alcohol consumption for association with gout (P = 8.2 x 10^-9). In the genotype-stratified association analysis, presence of the T allele at ADH1B rs1229984 was not associated with hyperuricaemia or gout in non-drinkers (Table 1). However, in the alcohol-exposed subgroup, the T-positive genotype was associated with increased hyperuricaemia and gout compared to the T-negative genotype. Similarly, LOC100507053 rs11733695 and ADH1C rs141973904 were only associated with hyperuricaemia among drinkers and not non-drinkers.

Conclusion: In this large study of European participants, novel interactions with alcohol consumption for hyperuricaemia or gout were identified at LOC100507053, ADH1B, and ADH1C. This may represent a single signal at ADH1B rs1229984 with linkage disequilibrium explaining the other two significant interactions. The association of ADH1B with serum urate levels and gout may occur through the modulation of alcohol metabolism rate among drinkers.
Table 1. Genotype-stratified association analysis of ADH1B rs1229984 and alcohol consumption for hyperuricaemia and gout.
Disclosures: M. Chuah, None; R. Topless, None; G. Gamble, None; N. Sumpter, None; L. Stamp, None; T. Merriman, None; N. Dalbeth, AstraZeneca, Dyve Biosciences, Horizon, Selecta, JW Pharmaceutical Corporation, PK Med, PTC Therapeutics, Protalix.