title: Association of functional polymorphism rs2231142 (Q141K) in the ABCG2 gene with serum uric acid and gout in 4 US populations: the PAGE Study.
abstract: A loss-of-function mutation (Q141K, rs2231142) in the ATP-binding cassette, subfamily G, member 2 gene (ABCG2) has been shown to be associated with serum uric acid levels and gout in Asians, Europeans, and European and African Americans; however, less is known about these associations in other populations. Rs2231142 was genotyped in 22,734 European Americans, 9,720 African Americans, 3,849 Mexican Americans, and 3,550 American Indians in the Population Architecture using Genomics and Epidemiology (PAGE) Study (2008-2012). Rs2231142 was significantly associated with serum uric acid levels (P = 2.37 × 10(-67), P = 3.98 × 10(-5), P = 6.97 × 10(-9), and P = 5.33 × 10(-4) in European Americans, African Americans, Mexican Americans, and American Indians, respectively) and gout (P = 2.83 × 10(-10), P = 0.01, and P = 0.01 in European Americans, African Americans, and Mexican Americans, respectively). Overall, the T allele was associated with a 0.24-mg/dL increase in serum uric acid level (P = 1.37 × 10(-80)) and a 1.75-fold increase in the odds of gout (P = 1.09 × 10(-12)). The association between rs2231142 and serum uric acid was significantly stronger in men, postmenopausal women, and hormone therapy users compared with their counterparts. The association with gout was also significantly stronger in men than in women. These results highlight a possible role of sex hormones in the regulation of ABCG2 urate transporter and its potential implications for the prevention, diagnosis, and treatment of hyperuricemia and gout.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Kylee L
authors.initials: KL
authors.lastname: Spencer
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Neal W
authors.initials: NW
authors.lastname: Jorgensen
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Lyle G
authors.initials: LG
authors.lastname: Best
authors.forename: Kristin D
authors.initials: KD
authors.lastname: Brown-Gentry
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Ewa
authors.initials: E
authors.lastname: Deelman
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Angelo L
authors.initials: AL
authors.lastname: Gaffo
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Glenn
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Anna
authors.initials: A
authors.lastname: Kottgen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Kiang
authors.initials: K
authors.lastname: Liu
authors.forename: Tara C
authors.initials: TC
authors.lastname: Matise
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D001741:Black or African American / Q000235:genetics; D017677:Age Distribution; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006073:Gout / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D020249:Hormone Replacement Therapy / Q000706:statistics & numerical data; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017678:Sex Distribution; D014481:United States; D014527:Uric Acid / Q000097:blood*; D044465:White People / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D014527:Uric Acid
keywords: ABCG2 protein, human; genetic association studies; gout; meta-analysis; polymorphism, single nucleotide; urate transporter; uric acid
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