POS0191 GENETIC EVIDENCE REVEALS A CAUSAL RELATIONSHIP BETWEEN TRIGLYCERIDE AND GOUT

Abstract

BackgroundGout is caused by hyperuricemia that leads to the formation and deposition of monosodium urate (MSU) crystals, which is characterized by acute episodes of joint inflammation [1]. Epidemiological studies observed increased levels of triglycerides in gout [2,3]. Triglyceride is a kind of adipokine primarily transported by very low-density lipoprotein. Enriched in very low-density lipoprotein triglycerides was significantly associated with gout in hyperuricemia [2]. However, the causal association between triglycerides and gout remains unclear.ObjectivesThis study aims to use a two-sample Mendelian randomization (MR) to examine associations of triglycerides with gout.MethodsSummary data for triglycerides used in this study were obtained from a genome-wide association study (GWAS), which included 441,016 European participants within the UK Biobank [4]. The gout GWAS datasets were from a large-scale meta-analysis, which included 69,374 individuals (2,115 cases and 67,259 controls) from European [5]. We selected genetic variation highly related to triglyceride (P＜5.00E-8, r2=0.001) as the potential instrumental variables. Three MR methods, namely inverse-variance weighted (IVW), weighted median, and MR-Egger, were applied for MR analysis. For sensitivity analysis, we used common statistical methods, namely Cochran’s Q test, MR-Egger intercept analysis, the funnel plot, and the leave-one-out analysis.ResultsAfter accounting for LD and the harmonization process, the total number of variants included in the MR investigating the effect of triglycerides on gout was 166. Triglycerides were a risk factor for gout (odds ratio (OR)=1.49, 95% confidence interval (CI):1.22-1.82, P=8.16E-05), which was consistent with the MR-Egger (OR=1.40, 95%CI:1.11-1.89, p= 2.93E-02). Cochran’s Q test and MR-Egger intercept showed no evidence of heterogeneity and horizontal pleiotropy (MR-Egger-intercept: 0.0025, P=0.583). The leave-one-out analysis also failed to detect any SNPs that may have a disproportional effect (Figure 1).Figure 1.MR analysis results for triglycerides and gout. (A) Scatter plot of single nucleotide polymorphism (SNP) potential effects on triglycerides and gout. The slope of fitted lines represents the estimated MR effect per method. (B) Funnel plot for triglycerides shows the estimation using the inverse of the standard error of the causal estimate with each individual SNP as a tool. (C) Forest plot showing MR analysis results to evaluate the causal association between triglycerides and gout using three methods.ConclusionTriglyceride was a hazard factor for gout, even in the absence of hyperuricemia, suggesting that controlling the level of triglyceride and paying attention to diet may be beneficial to prevent the occurrence of gout.