Interaction of the TRIM46 / MUC1 locus with cigarette smoking may influence the risk of gout.

Objectives: Some studies suggest that current-smoking may be protective against gout and smoking cessation associated with higher incidence of gout. Our study assessed potential interactions between smoking, genetic variants and gout prevalence. Methods: : Four loci ( ABCG2 , GCKR , TRIM46, HNF4G ) with evidence of smoking-influenced associations with serum urate were tested for non-additive interaction with current-smoker or ex-smoker status that associates with gout in Aotearoa New Zealand (NZ) East and West Polynesian participants with (n=520) and without (n=629) gout. Results: : Ex-smoker status was associated with higher prevalence of gout in people with East Polynesian but not West Polynesian ancestry. No association was detected between current smoking and gout. An interaction between TRIM46 (rs11264341) and ex-smoker status that associates with gout was observed in meta-analysis of NZ East and West Polynesians [OR Interaction = 0.58 (0.37-0.92)]. Never-smokers who were homozygous for the rs11264341 C-allele had higher odds of gout [OR= 2.43 (1.27; 4.64)], but not never-smoker heterozygotes [1.20 (0.73; 1.97]. The C allele was not associated with gout in ex-smokers [0.73 (0.36-1.47)]. No interactions involving current-smoker status were detected. Conclusions: : We provide evidence for a non-additive interaction between TRIM46 (rs11264341) and ex-smoker status that associated with gout prevalence. MUC1 , which encodes a transmembrane mucin in the lungs affected by cigarette smoke, is a possible candidate gene at this locus. No interaction involving current-smoker status was observed raising uncertainties about the relevance of an interaction specific to ex-smokers.