Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk

J Hum Genet. 2016 Sep;61(9):803-10. doi: 10.1038/jhg.2016.57. Epub 2016 May 26.

Abstract

The aim of the present study was to evaluate the contribution of urate transporter genes and alcohol use to the risk of gout/tophi. Eight variants of ABCG2, SLC2A9, SLC22A12, SLC22A11 and SLC17A3 were genotyped in male individuals in a case-control study with 157 gout (33% tophi), 106 asymptomatic hyperuricaemia and 295 control subjects from Taiwan. The multilocus profiles of the genetic risk scores for urate gene variants were used to evaluate the risk of asymptomatic hyperuricaemia, gout and tophi. ABCG2 Q141K (T), SLC2A9 rs1014290 (A) and SLC22A12 rs475688 (C) under an additive model and alcohol use independently predicted the risk of gout (respective odds ratio for each factor=2.48, 2.03, 1.95 and 2.48). The additive composite Q141K, rs1014290 and rs475688 scores of high-risk alleles were associated with gout risk (P<0.0001). We observed the supramultiplicative interaction effect of genetic urate scores and alcohol use on gout and tophi risk (P for interaction=0.0452, 0.0033). The synergistic effect of genetic urate score 5-6 and alcohol use indicates that these combined factors correlate with gout and tophi occurrence.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
  • Adult
  • Age of Onset
  • Aged
  • Alcohol Drinking / adverse effects*
  • Alleles*
  • Case-Control Studies
  • Comorbidity
  • Genotype
  • Glucose Transport Proteins, Facilitative / genetics*
  • Gout / epidemiology*
  • Gout / etiology*
  • Humans
  • Hyperuricemia / epidemiology
  • Hyperuricemia / genetics
  • Male
  • Middle Aged
  • Odds Ratio
  • Organic Anion Transporters / genetics*
  • Organic Cation Transport Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Risk
  • Taiwan / epidemiology

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Glucose Transport Proteins, Facilitative
  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • SLC22A12 protein, human
  • SLC2A9 protein, human