Genetically predicted serum uric acid levels and the risk of coronary artery disease in patients with diabetes: A Mendelian randomization study

Abstract

Background and aims: Serum uric acid (SUA) levels have been reported to be associated with an increased risk of coronary artery disease (CAD) among patients with diabetes in observational study. Whether this relationship is causal remains unclear. The current study aimed to explore the causal association between SUA and the risk of CAD in patients with diabetes. Methods and results: A two-sample Mendelian randomization (MR) approach was employed to evaluate the causal effect of SUA on the risk of CAD in patients with diabetes. A total of 28 single nucleotide polymorphisms (SNPs) related to SUA were identified as instruments. Genetic association with CAD were obtained from a recently published genome-wide association study (GWAS) of 15,666 patients with diabetes (3968 CAD cases and 11,696 controls). The fixed-effects inverse variance-weighted method was employed to estimate the causal effect for the primary analysis, and other robust methods were employed for sensitivity analyses. In addition, the whole analyses were repeated using 9 non-pleiotropic SNPs. Genetic determined SUA levels were not significantly associated with the risk of CAD in patients with diabetes in the primary analysis (odds ratio Z 1.13, 95% confidence interval: 0.98e1.16, P Z 0.09). Consistent results were observed in the sensitivity analyses using various robust methods. In addition, this finding was confirmed by the repeated analyses using 9 non-pleiotropic SNPs. Conclusions: This two-sample MR study does not support a causal effect of genetically predicted SUA levels on the risk of CAD in patients with diabetes.

Sex-specific effect of serum urate levels on coronary heart disease and myocardial infarction prevention: A Mendelian randomization study

“…A previous MR study investigated the causality between serum urate levels and several cardiometabolic diseases using 14 single nucleotide polymorphisms (SNPs) in a genetic risk score, and found no evidence for the causal role of serum urate levels in CHD [17]. Using MR methods, we also found weak evidence for the causal effect of genetically predicted serum urate level on the risk of CHD in patients with diabetes before [18]. Meanwhile, few MR studies had investigated the sex-specific effect of serum urate on CHD or MI and the causal role of serum urate in individuals of non-European ancestry.…”

Association between glucokinase regulator gene polymorphisms and serum uric acid levels in Taiwanese adolescents

“…Conversely, other MR studies did not support this finding. In a two-sample MR study, the serum UA levels were not significantly associated with the risk of coronary artery disease (CAD) in European patients with diabetes 45 . Another MR study did not support the causal function of the elevated serum UA levels in premature CAD in the Mexican population 46 .…”