A Meta-analysis of the Associations Between the Q141K and Q126X ABCG2 Gene Variants and Gout Risk

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2015 Dec 1

PMID 26617691

Citations 19

Authors

Rui Li

Lei Miao

Liyan Qin

Yang Xiang

Xiaojin Zhang

Hui Peng

Mailamuguli

Yuping Sun

Hua Yao

Affiliations

Soon will be listed here.

Abstract

Background: Gout is an inflammatory disease in which genetic factors play a role. ABCG2 is a urate transporter, and the Q141K and Q126X variants of ABCG2 have been associated with a risk of developing gout, though previous studies of these associations have been inconsistent. Therefore, we conducted a meta-analysis to explore the relationship between these genetic variants and gout.

Methods: We examined 8 electronic literature databases. In total, 9 eligible articles on the associations between the Q141K (rs2231142) and Q126X (rs72552713) variants and gout risk, including 11 case-control studies were selected. We used odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of these relationships in dominant, recessive, and co-dominant models.

Results: This study included 6652 participants (2499 gout patients and 4153 controls). The Q141K variant was found to significantly increase the risk of gout in Asians (dominant model: OR=2.64, 95% CI=2.04-3.43, P=0.02 for heterogeneity; recessive model: OR=3.19, 95% CI=2.56-3.97, P=0.28 for heterogeneity; co-dominant model: OR=1.37, 95% CI=1.18-1.59, P=0.09 for heterogeneity) and other populations (dominant model: OR=1.85, 95% CI=1.20-2.85, P<0.0001 for heterogeneity; recessive model: OR=3.78, 95% CI=2.28-6.27, P=0.19 for heterogeneity; co-dominant model: OR=1.48, 95% CI=1.26-1.74, P=0.19 for heterogeneity). The Q126X variant also significantly increased the risk of gout in Asians (dominant model: OR=3.87, 95% CI=2.07-7.24, P=0.06 for heterogeneity).

Conclusions: These results suggest associations between the rs2231142 and rs72552713 ABCG2 gene polymorphisms and gout risk, which led to unfavorable outcomes. However, studies with larger sample sizes and homogeneous populations should be performed to confirm these results.

Citing Articles

A combination of red and processed meat intake and polygenic risk score influences the incidence of hyperuricemia in middle-aged Korean adults.

Lee S, Shin D Nutr Res Pract. 2024; 18(5):721-745.

PMID: 39398885 PMC: 11464275. DOI: 10.4162/nrp.2024.18.5.721.

Examining the Association of Rare Allelic Variants in Urate Transporters , , and with Hyperuricemia and Gout.

Vavra J, Pavelcova K, Masinova J, Hasikova L, Bubenikova E, Urbanova A Dis Markers. 2024; 2024:5930566.

PMID: 38222853 PMC: 10787658. DOI: 10.1155/2024/5930566.

Cannabis Pharmacogenomics: A Path to Personalized Medicine.

Babayeva M, Loewy Z Curr Issues Mol Biol. 2023; 45(4):3479-3514.

PMID: 37185752 PMC: 10137111. DOI: 10.3390/cimb45040228.

ABCG2 in Acute Myeloid Leukemia: Old and New Perspectives.

Damiani D, Tiribelli M Int J Mol Sci. 2023; 24(8).

PMID: 37108308 PMC: 10138346. DOI: 10.3390/ijms24087147.

Dutch pharmacogenetics working group guideline for the gene-drug interaction of ABCG2, HLA-B and Allopurinol, and MTHFR, folic acid and methotrexate.

van der Pol K, Nijenhuis M, Soree B, de Boer-Veger N, Buunk A, Guchelaar H Eur J Hum Genet. 2022; 32(2):155-162.

PMID: 36056234 PMC: 10853275. DOI: 10.1038/s41431-022-01180-0.

References

Yamagishi K, Tanigawa T, Kitamura A, Kottgen A, Folsom A, Iso H . The rs2231142 variant of the ABCG2 gene is associated with uric acid levels and gout among Japanese people. Rheumatology (Oxford). 2010; 49(8):1461-5. DOI: 10.1093/rheumatology/keq096. View

Matsuo H, Nakayama A, Sakiyama M, Chiba T, Shimizu S, Kawamura Y . ABCG2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload. Sci Rep. 2014; 4:3755. PMC: 3895923. DOI: 10.1038/srep03755. View

Dong Z, Guo S, Yang Y, Wu J, Guan M, Zou H . Association between ABCG2 Q141K polymorphism and gout risk affected by ethnicity and gender: a systematic review and meta-analysis. Int J Rheum Dis. 2015; 18(4):382-91. DOI: 10.1111/1756-185X.12519. View

Wallace S, Robinson H, MASI A, Decker J, McCarty D, Yu T . Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977; 20(3):895-900. DOI: 10.1002/art.1780200320. View

Stark K, Reinhard W, Grassl M, Erdmann J, Schunkert H, Illig T . Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease. PLoS One. 2009; 4(11):e7729. PMC: 2766838. DOI: 10.1371/journal.pone.0007729. View

Zhang L, Spencer K, Saroja Voruganti V, Jorgensen N, Fornage M, Best L . 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; 177(9):923-32. PMC: 4023295. DOI: 10.1093/aje/kws330. View

Little J, Higgins J, Ioannidis J, Moher D, Gagnon F, von Elm E . STrengthening the REporting of Genetic Association Studies (STREGA): an extension of the STROBE statement. PLoS Med. 2009; 6(2):e22. PMC: 2634792. DOI: 10.1371/journal.pmed.1000022. View

Lee J, Lee J, Lee J, Jung S, Suh Y, Koh J . Visceral fat obesity is highly associated with primary gout in a metabolically obese but normal weighted population: a case control study. Arthritis Res Ther. 2015; 17:79. PMC: 4381370. DOI: 10.1186/s13075-015-0593-6. View

Li F, Chu Y, Meng D, Tong Y . [Association of ABCG2 gene C421A polymorphism and susceptibility of primary gout in Han Chinese males]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2011; 28(6):683-5. DOI: 10.3760/cma.j.issn.1003-9406.2011.06.019. View

10.

Dehghan A, Kottgen A, Yang Q, Hwang S, Kao W, Rivadeneira F . Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 2008; 372(9654):1953-61. PMC: 2803340. DOI: 10.1016/S0140-6736(08)61343-4. View

11.

Hak A, Curhan G, Grodstein F, Choi H . Menopause, postmenopausal hormone use and risk of incident gout. Ann Rheum Dis. 2009; 69(7):1305-9. PMC: 3142742. DOI: 10.1136/ard.2009.109884. View

12.

Matsuo H, Ichida K, Takada T, Nakayama A, Nakashima H, Nakamura T . Common dysfunctional variants in ABCG2 are a major cause of early-onset gout. Sci Rep. 2013; 3:2014. PMC: 3684804. DOI: 10.1038/srep02014. View

13.

Roddy E, Choi H . Epidemiology of gout. Rheum Dis Clin North Am. 2014; 40(2):155-75. PMC: 4119792. DOI: 10.1016/j.rdc.2014.01.001. View

14.

Flynn T, Phipps-Green A, Hollis-Moffatt J, Merriman M, Topless R, Montgomery G . Association analysis of the SLC22A11 (organic anion transporter 4) and SLC22A12 (urate transporter 1) urate transporter locus with gout in New Zealand case-control sample sets reveals multiple ancestral-specific effects. Arthritis Res Ther. 2013; 15(6):R220. PMC: 3978909. DOI: 10.1186/ar4417. View

15.

Matsuo H, Tomiyama H, Satake W, Chiba T, Onoue H, Kawamura Y . ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout. Ann Clin Transl Neurol. 2015; 2(3):302-6. PMC: 4369280. DOI: 10.1002/acn3.167. View

16.

Soriano L, Rothenbacher D, Choi H, Garcia Rodriguez L . Contemporary epidemiology of gout in the UK general population. Arthritis Res Ther. 2011; 13(2):R39. PMC: 3132018. DOI: 10.1186/ar3272. View

17.

Maynard J, McAdams-DeMarco M, Law A, Kao L, Gelber A, Coresh J . Racial differences in gout incidence in a population-based cohort: Atherosclerosis Risk in Communities Study. Am J Epidemiol. 2013; 179(5):576-83. PMC: 3927975. DOI: 10.1093/aje/kwt299. View

18.

Li C, Chu N, Wang B, Wang J, Luan J, Han L . Polymorphisms in the presumptive promoter region of the SLC2A9 gene are associated with gout in a Chinese male population. PLoS One. 2012; 7(2):e24561. PMC: 3290627. DOI: 10.1371/journal.pone.0024561. View

19.

Hollis-Moffatt J, Phipps-Green A, Chapman B, Jones G, van Rij A, Gow P . The renal urate transporter SLC17A1 locus: confirmation of association with gout. Arthritis Res Ther. 2012; 14(2):R92. PMC: 3446466. DOI: 10.1186/ar3816. View

20.

Phipps-Green A, Hollis-Moffatt J, Dalbeth N, Merriman M, Topless R, Gow P . A strong role for the ABCG2 gene in susceptibility to gout in New Zealand Pacific Island and Caucasian, but not Māori, case and control sample sets. Hum Mol Genet. 2010; 19(24):4813-9. DOI: 10.1093/hmg/ddq412. View