title: SLC2A9 influences uric acid concentrations with pronounced sex-specific effects.
abstract: Serum uric acid concentrations are correlated with gout and clinical entities such as cardiovascular disease and diabetes. In the genome-wide association study KORA (Kooperative Gesundheitsforschung in der Region Augsburg) F3 500K (n = 1,644), the most significant SNPs associated with uric acid concentrations mapped within introns 4 and 6 of SLC2A9, a gene encoding a putative hexose transporter (effects: -0.23 to -0.36 mg/dl per copy of the minor allele). We replicated these findings in three independent samples from Germany (KORA S4 and SHIP (Study of Health in Pomerania)) and Austria (SAPHIR; Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk), with P values ranging from 1.2 x 10(-8) to 1.0 x 10(-32). Analysis of whole blood RNA expression profiles from a KORA F3 500K subgroup (n = 117) showed a significant association between the SLC2A9 isoform 2 and urate concentrations. The SLC2A9 genotypes also showed significant association with self-reported gout. The proportion of the variance of serum uric acid concentrations explained by genotypes was about 1.2% in men and 6% in women, and the percentage accounted for by expression levels was 3.5% in men and 15% in women.
authors.affiliation: Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Döring
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Divya
authors.initials: D
authors.lastname: Mehta
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: Stefan
authors.initials: S
authors.lastname: Coassin
authors.forename: Guido
authors.initials: G
authors.lastname: Fischer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Henke
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.forename: Arne
authors.initials: A
authors.lastname: Pfeufer
authors.forename: Dieter
authors.initials: D
authors.lastname: Rosskopf
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019295:Computational Biology; D005260:Female; D015894:Genome, Human; D005838:Genotype; D005858:Germany; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006073:Gout / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017678:Sex Distribution; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid