Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration

PLoS One. 2014 May 14;9(5):e97646. doi: 10.1371/journal.pone.0097646. eCollection 2014.

Abstract

Objective: Uric 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.

Methods: The 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.

Results: The 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.

Conclusion: Metabolic 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / blood*
  • ATP-Binding Cassette Transporters / genetics
  • Adolescent
  • Adult
  • Aged
  • Alcohol Drinking / blood*
  • Alcohol Drinking / genetics
  • Alcohol Drinking / pathology
  • Cohort Studies
  • Female
  • Gene Expression
  • Glucose Transport Proteins, Facilitative / blood
  • Glucose Transport Proteins, Facilitative / genetics
  • Humans
  • Male
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / pathology
  • Methylenetetrahydrofolate Reductase (NADPH2) / blood
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Models, Genetic
  • Neoplasm Proteins / blood*
  • Neoplasm Proteins / genetics
  • Polymorphism, Single Nucleotide*
  • Regression Analysis
  • Sex Factors
  • Uric Acid / blood*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Glucose Transport Proteins, Facilitative
  • Neoplasm Proteins
  • SLC2A9 protein, human
  • Uric Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)

Grant support

This study was supported by a grant from the Czech Republic Ministry of Health (IGA MZ NT/11322–4/2010 and RVO VFN64165) and by institutional support from a program at Charles University in Prague (PRVOUK-P24/LF1/3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.