Association of Functional Polymorphism rs2231142 (Q141K) in the ABCG2 Gene With Serum Uric Acid and Gout in 4 US Populations The PAGE Study

• Published in: American journal of epidemiology Vol. 177; no. 9; pp. 923 - 932
• Main Authors: LILI ZHANG, SPENCER, Kylee L, FRANCESCHINI, Nora, GAFFO, Angelo L, GLENN, Kimberly R, HEISS, Gerardo, JENNY, Nancy S, KOTTGEN, Anna, QIONG LI, KIANG LIU, MATISE, Tara C, NORTH, Kari E, VORUGANTI, V. Saroja, UMANS, Jason G, LINDA KAO, W. H, JORGENSEN, Neal W, FORNAGE, Myriam, BEST, Lyle G, BROWN-GENTRY, Kristin D, COLE, Shelley A, CRAWFORD, Dana C, DEELMAN, Ewa
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01-05-2013
• Series: Editor's choice
• Subjects: Adult; African Americans - genetics; Age Distribution; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; Comorbidity; Diseases of the osteoarticular system; Epidemiology; European Continental Ancestry Group - genetics; Female; General aspects; Genetic Predisposition to Disease; Genetics, Population; Genome-Wide Association Study; Gout - blood; Gout - ethnology; Gout - genetics; Hormone Replacement Therapy - statistics & numerical data; Humans; Indians, North American - genetics; Inflammatory joint diseases; Male; Medical sciences; Metabolic diseases; Mexican Americans - genetics; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Neoplasm Proteins - genetics; Original Contributions; Other metabolic disorders; Polymorphism, Genetic; Postmenopause; Public health. Hygiene; Public health. Hygiene-occupational medicine; Purines and pyrimidines (gout, hyperuricemia...); Sex Distribution; United States; Uric Acid - blood; United States; North America; America; Gout; Diseases of the osteoarticular system; urate transporter; Epidemiology; Evidence-based medicine; Metaanalysis; Hyperuricemia; ABCG2 protein; Association; Gene; Genetics; Serum; Public health; Human; Evidence-based practice; meta-analysis; Metabolic diseases; Uric acid; Microcristalline arthropathy; Protein; Nucleotide; single nucleotide; Purine; genetic association studies; Microcrystal; Polymorphism; ABCG2 protein, human; gout; polymorphism, single nucleotide; uric acid
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/aje/kws330

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.