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.
Highlights
An increased serum uric acid (UA) concentration (.416 mmol/ L in men and .340 mmol/L in children and women) is an important risk factor for gout and has other significant associations with human disorders, such as cardiovascular and renal diseases [1,2]
Our study was aimed at answering the following unresolved questions: (a) What is the relationship between serum UA and demographic, anthropometric and other variables? (b) What is the relationship between serum UA and metabolic syndrome? (c) What is the influence of genetic determinants on serum UA? In our study, we examined the associations between serum UA concentrations and a wide range of variables in a cohort from central Europe
We modeled the associations between UA and (i) demographic, anthropometric and other variables previously reported to be associated with serum UA; (ii) the presence of metabolic syndrome (MS) and the levels of MS components and (iii) selected genetic variants in the SLC2A9, ABCG2 and MTHFR genes
Summary
An increased serum uric acid (UA) concentration (.416 mmol/ L in men and .340 mmol/L in children and women) is an important risk factor for gout and has other significant associations with human disorders, such as cardiovascular and renal diseases [1,2]. Serum UA concentrations have been linked to many ageing-related illnesses and to brain function, the direction of the association is unclear. It has been suggested that higher UA concentrations may be associated with increased performance on memory-related tasks [5]. Data from numerous studies suggest that serum UA concentrations are markedly heritable; the proportion of variance explained by a shared genetic background ranges from 0.38–0.63 [12,13,14,15]
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