Metabolic Syndrome, Alcohol Consumption and Genetic Factors Are Associated with Serum Uric Acid Concentration

Abstract

ObjectiveUric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals.MethodsThe cohort consisted of 589 healthy subjects aged 18–65 years. We studied the associations between the serum uric acid concentration and the following: (i) demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii) the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii) selected genetic variants of the MTHFR (c.665C>T, c.1286A>C), SLC2A9 (c.844G>A, c.881G>A) and ABCG2 genes (c.421C>A). A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables.ResultsThe models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations.ConclusionMetabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

Inhibition of sterile danger signals, uric acid and ATP, prevents inflammasome activation and protects from alcoholic steatohepatitis in mice

“…Our data is consistent with previously published experimental evidence supporting a causal role of ATP or uric acid signaling in liver inflammation caused by acetaminophen or by ischemia-reperfusion injury [8, 24, 25], and are further supported by evidence showing correlation between hyperuricemia and metabolic syndrome or long-term consumption of ethanol [26, 27]. Importantly, our data is consistent with a report by Shulga et al [28] demonstrating that activation of murine Kupffer cells by ethanol requires NLRP3, a ligand-sensing component of inflammasomes that detects ATP and uric acid [5].…”

Causal effect of alcohol consumption on hyperuricemia using a Mendelian randomization design

“…Previous genetic studies have demonstrated the associations between alcohol use and UA in humans . To the best of our knowledge, our study is the first to perform a Mendelian randomization analysis showing a potential causal association of increased alcohol use and higher UA.…”

The association between risk of airflow limitation and serum uric acid measured at medical health check-ups

“…This may have influenced the overall difference in parameters relevant to CADs. Second, we could not completely rule out all possible factors that may influence s-UA levels, including chronic kidney disorders, genetic disorders of purine metabolism, cardiovascular diseases, food intake, metabolic syndrome, and alcohol consumption 27,36,37. However, even after adjusting for possible and major confounding factors (age, gender, BMI, and smoking index), logistic regression analysis showed that s-UA levels continued to be an independent predictor of AL risk.…”