ABCMdb

PMID: 23552988

Zhang L, Spencer KL, Voruganti VS, Jorgensen NW, Fornage M, Best LG, Brown-Gentry KD, Cole SA, Crawford DC, Deelman E, Franceschini N, Gaffo AL, Glenn KR, Heiss G, Jenny NS, Kottgen A, Li Q, Liu K, Matise TC, North KE, Umans JG, Kao WH
Association of functional polymorphism rs2231142 (Q141K) in the ABCG2 gene with serum uric acid and gout in 4 US populations: the PAGE Study.
Am J Epidemiol. 2013 May 1;177(9):923-32. doi: 10.1093/aje/kws330. Epub 2013 Apr 3., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCG2 p.Gln141Lys 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. Login to comment 27 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys More importantly, the resultant missense polymorphism at codon 141 (glutamine to lysine, Q141K) has been shown to be a loss-of-function mutation in 2 independent functional studies (22, 23). Login to comment 134 ABCG2 p.Gln141Lys DISCUSSION In a meta-analysis of 39,853 persons from 4 different population-based samples (European Americans, African Americans, Mexican Americans, and American Indians), we demonstrated that the functional variant rs2231142 (Q141K) in the ABCG2 gene was significantly associated with both serum uric acid level (P = 2.37 &#d7; 10-67 , P = 3.98 &#d7; 10-5 , P = 6.97 &#d7; 10-9 , and P = 5.33 &#d7; 10-4 in European Americans, African Americans, Mexican Americans, and American Indians, respectively) and the odds of Table 3. Login to comment 148 ABCG2 p.Gln141Lys The Q141K (rs2231142) polymorphism occurs in a highly conserved region of the gene and has been shown to be a loss-of-function mutation in 2 independent functional studies (22, 23). Login to comment 156 ABCG2 p.Gln141Lys systems are reflective of the human kidney, one might expect that the consequence of the Q141K loss-of-function polymorphism would be relatively less in persons with high estrogen levels (they had decreased ABCG2 mRNA expression to begin with) compared with those with low estrogen levels. Login to comment 176 ABCG2 p.Gln141Lys Lastly, the Q141K variant is a well-studied functional polymorphism, thus providing a strong a priori hypothesis and biological plausibility. Login to comment 178 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys In conclusion, the common polymorphism rs2231142, which leads to a change from glutamine to lysine in codon 141 (Q141K) of the ABCG2 gene, is significantly associated with elevated serum uric acid levels and increased prevalence of gout in European Americans, African Americans, Mexican Americans, and Americans Indians. Login to comment