title: Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk.
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.
authors.affiliation: Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Pin
authors.initials: HP
authors.lastname: Tu
authors.affiliation: Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chung
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Min-Shan Ko
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Su-Shin
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Lai
authors.affiliation: Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Huang
authors.affiliation: Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chiu-Shong
authors.initials: CS
authors.lastname: Liu
authors.affiliation: Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D000483:Alleles; D016022:Case-Control Studies; D015897:Comorbidity; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006073:Gout / Q000453:epidemiology* / Q000209:etiology*; D006801:Humans; D033461:Hyperuricemia / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D051246:Glucose Transport Proteins, Facilitative; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; C411811:SLC2A9 protein, human