THE ABCG2 RS2231142 POLYMORPHISM ARE ASSOCIATED WITH RISK OF NEPHROLITHIASIS IN A TAIWANESE POPULATION.

BackgroundIn genome-wide association studies (GWAS), the strong association of ABCG2 rs2231142 variant with hyperuricemia and gout was confirmed in Asian population. Additionally, the obesity, diet, lifestyle, genetics and underlying comorbidities are important risks factors predisposing to hyperuricemia and gout. The systematic reviews revealed a significant link between obesity, systemic comorbidities and hyperuricosuria for predisposition of kidney stones (nephrolithiasis). However, whether ABCG2 plays an important role in the phathogenesis of nephrolithiasis remain unclear. The interaction between genetic factors and other risk factors of nephrolithiasis is still elusive.ObjectivesIn this study, we want to explore the association between ABCG2 rs2231142 variant and the risk of nephrolithiasis in modern Taiwanese population, and clarify the role of uric acid in nephrolithiasis formation.MethodsThis retrospective case-control study was conducted using the Taiwan Biobank database. A total of 120,267 individuals of Taiwanese Han Chinese aged 30-70 years were enrolled in the study. The primary outcome was the incidence of self-reported nephrolithiasis. Odds ratio (OR) of incident nephrolithiasis was analyzed by multiple logistic regression models and the interaction between ABCG2 rs2231142 variants, serum uric acid level, on the nephrolithiasis was explored. The multifactorial confounding factors for prediction of nephrolithiasis were also re-examined in our study.ResultsFinally, we identified 8,410 participants with nephrolithiasis and the prevalence was 11.52% and 4.37% in men and women, respectively. Older age (OR=1.08, 95% CI: 1.02-1.03, p<0.001) and male gender (OR=2.21, 95% CI: 2.08-2.36, p<0.001) showed an independent predictor for development of incident nephrolithiasis. The risk of nephrolithiasis markedly increased resulting from the interaction of ABCG2 rs2231142 and nephrolithiasis. In comparison with GG genotype, the risk of nephrolithiasis also demonstrated a significant association with TT and GT genotype (TT: OR=1.18, 95% CI: 1.09-1.28, p<0.001; GT: OR=1.12, 95% CI: 1.06-1.18, p<0.001). The variant comorbidities significantly associated with susceptibility to nephrolithiasis are hyperlipidemia (OR=1.40, 95% CI: 1.29-1.51, p<0.001), hypertension (OR=1.67, 95% CI: 1.57-1.78, p<0.001), diabetes mellitus (OR=1.16, 95% CI: 1.06-1.26, p=0.002), and hyperuricemia (OR=1.06, 95% CI: 1.04-1.08, p<0.001) with significant difference. The interaction of lifestyles and the risk of nephrolithiasis revealed significant differences in smoking (OR=1.15, 95% CI: 1.09-1.22, p<0.001) and overweight (OR=1.22, 95% CI: 1.15-1.28, p<0.001) rather than alcohol use(OR=0.92, 95% CI: 0.84-1.01, p=0.083). Participants with regular physical exercise is a protective factor from nephrolithiasis (OR=0.95, 95% CI:0.9-1.0, p=0.048).ConclusionOur study demonstrated the risk of nephrolithiasis is significant association with ABCG2 rs2231142 variants. This risk also increased with systemic comorbidities (hyperlipidemia, hypertension, diabetes mellitus, and hyperuricemia), and lifestyle (obesity, and smoking). Regular physical exercise is associated with protective factor for incident nephrolithiasis.Table 1.Adjusted Odds ratio of kidney stone.VariableOR95% CIp-valueAge, years1.03(1.02-1.03)<0.001Gender female1.00—— male2.21(2.08-2.36)<0.001ABCG2 rs2231142 GG1.00—— GT1.12(1.06-1.18)<0.001 TT1.18(1.09-1.28)<0.001Hyperlipidemia No1.00—— Yes1.40(1.29-1.51)<0.001Hypertension No1.00—— Yes1.67(1.57-1.78)<0.001Diabetes No1.00—— Yes1.16(1.06-1.26)0.002Hyperuricemia >7.0 mg/dL No1.00—— Yes1.06(1.04-1.08)<0.001Smoking No1.00—— Yes1.15(1.09-1.22)<0.001Alcohol use No1.00—— Yes0.92(0.84-1.01)0.083Regular physical exercise No1.00—— Yes0.95(0.90-1.00)0.048Overweight, BMI ≥24 kg/m2 No1.00—— Yes1.22(1.15-1.28)<0.001OR was adjusted for all variables in table.Disclosure of InterestsNone declared