The Association Between Genetic Polymorphisms in ABCG2 and SLC2A9 and Urate: an Updated Systematic Review and Meta-analysis

Overview

Journal BMC Med Genet

Publisher Biomed Central

Specialty Genetics

Date 2020 Oct 22

PMID 33087043

Citations 11

Authors

Thitiya Lukkunaprasit

Sasivimol Rattanasiri

Saowalak Turongkaravee

Naravut Suvannang

Atiporn Ingsathit

John Attia

Ammarin Thakkinstian

Affiliations

Soon will be listed here.

Abstract

Background: Replication studies showed conflicting effects of ABCG2 and SLC2A9 polymorphisms on gout and serum urate. This meta-analysis therefore aimed to pool their effects across studies.

Methods: Studies were located from MEDLINE and Scopus from inception to 17th June 2018. Observational studies in adults with any polymorphism in ABCG2 or SLC2A9, and outcome including gout, hyperuricemia, and serum urate were included for pooling. Data extractions were performed by two independent reviewers. Genotype effects were pooled stratified by ethnicity using a mixed-effect logistic model and a multivariate meta-analysis for dichotomous and continuous outcomes.

Results: Fifty-two studies were included in the analysis. For ABCG2 polymorphisms, mainly studied in Asians, carrying 1-2 minor-allele-genotypes of rs2231142 and rs72552713 were respectively about 2.1-4.5 and 2.5-3.9 times higher odds of gout than non-minor-allele-genotypes. The two rs2231142-risk-genotypes also had higher serum urate about 11-18 μmol/l. Conversely, carrying 1-2 minor alleles of rs2231137 was about 36-57% significantly lower odds of gout. For SLC2A9 polymorphisms, mainly studied in Caucasians, carrying 1-2 minor alleles of rs1014290, rs6449213, rs6855911, and rs7442295 were about 25-43%, 31-62%, 33-64%, and 35-65% significantly lower odds of gout than non-minor-allele-genotypes. In addition, 1-2 minor-allele-genotypes of the latter three polymorphisms had significantly lower serum urate about 20-49, 21-51, and 18-54 μmol/l than non-minor-allele-genotypes.

Conclusions: Our findings should be useful in identifying patients at risk for gout and high serum urate and these polymorphisms may be useful in personalized risk scores.

Trial Registration: PROSPERO registration number: CRD42018105275 .

Citing Articles

The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications.

Du J, Shen M, Chen J, Yan H, Xu Z, Yang X Front Pharmacol. 2025; 15():1510080.

PMID: 39850557 PMC: 11754210. DOI: 10.3389/fphar.2024.1510080.

U-shaped association of uric acid to HDL cholesterol ratio (UHR) with ALL-cause and cardiovascular mortality in diabetic patients: NHANES 1999-2018.

Huang X, Hu L, Li J, Wang X BMC Cardiovasc Disord. 2024; 24(1):744.

PMID: 39725874 PMC: 11674183. DOI: 10.1186/s12872-024-04436-3.

Development and Validation of a Literature Screening Tool: Few-Shot Learning Approach in Systematic Reviews.

Wiwatthanasetthakarn P, Ponthongmak W, Looareesuwan P, Tansawet A, Numthavaj P, Mckay G J Med Internet Res. 2024; 26():e56863.

PMID: 39662894 PMC: 11669879. DOI: 10.2196/56863.

Polymorphism rs3733591 of the gene and metabolic syndrome affect gout risk in Taiwan Biobank subjects.

Lin C, Ho C, Hsieh P, Hsiao C, Nfor O, Liaw Y Front Genet. 2024; 15:1374405.

PMID: 38689651 PMC: 11058208. DOI: 10.3389/fgene.2024.1374405.

The role of high fat diet on serum uric acid level among healthy male first degree relatives of type 2 diabetes mellitus.

Purnamasari D, Umpuan A, Tricaesario C, Wisnu W, Tarigan T, Tahapary D Sci Rep. 2023; 13(1):17586.

PMID: 37845387 PMC: 10579419. DOI: 10.1038/s41598-023-44843-8.

References

Furukawa T, Wakabayashi K, Tamura A, Nakagawa H, Morishima Y, Osawa Y . Major SNP (Q141K) variant of human ABC transporter ABCG2 undergoes lysosomal and proteasomal degradations. Pharm Res. 2008; 26(2):469-79. PMC: 2628956. DOI: 10.1007/s11095-008-9752-7. View

Stiburkova B, Pavelcova K, Pavlikova M, Jesina P, Pavelka K . The impact of dysfunctional variants of ABCG2 on hyperuricemia and gout in pediatric-onset patients. Arthritis Res Ther. 2019; 21(1):77. PMC: 6425717. DOI: 10.1186/s13075-019-1860-8. View

Testa A, Mallamaci F, Spoto B, Pisano A, Sanguedolce M, Tripepi G . Association of a polymorphism in a gene encoding a urate transporter with CKD progression. Clin J Am Soc Nephrol. 2014; 9(6):1059-65. PMC: 4046734. DOI: 10.2215/CJN.11041013. View

Wang B, Miao Z, Liu S, Wang J, Zhou S, Han L . Genetic analysis of ABCG2 gene C421A polymorphism with gout disease in Chinese Han male population. Hum Genet. 2009; 127(2):245-6. DOI: 10.1007/s00439-009-0760-4. View

Doring A, Gieger C, Mehta D, Gohlke H, Prokisch H, Coassin S . SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nat Genet. 2008; 40(4):430-6. DOI: 10.1038/ng.107. View

Wan W, Xu X, Zhao D, Pang Y, Wang Y . Polymorphisms of uric transporter proteins in the pathogenesis of gout in a Chinese Han population. Genet Mol Res. 2015; 14(1):2546-50. DOI: 10.4238/2015.March.30.13. View

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

Bartakova V, Kuricova K, Pacal L, Nova Z, Dvorakova V, Svrckova M . Hyperuricemia contributes to the faster progression of diabetic kidney disease in type 2 diabetes mellitus. J Diabetes Complications. 2016; 30(7):1300-7. DOI: 10.1016/j.jdiacomp.2016.06.002. View

Hu M, Tomlinson B . Gender-dependent associations of uric acid levels with a polymorphism in SLC2A9 in Han Chinese patients. Scand J Rheumatol. 2012; 41(2):161-3. DOI: 10.3109/03009742.2011.637952. View

10.

Tu H, Chen C, Tovosia S, Ko A, Lee C, Ou T . Associations of a non-synonymous variant in SLC2A9 with gouty arthritis and uric acid levels in Han Chinese subjects and Solomon Islanders. Ann Rheum Dis. 2009; 69(5):887-90. DOI: 10.1136/ard.2009.113357. View

11.

Zhang X, Yang X, Wang M, Li X, Xia Q, Xu S . Association between SLC2A9 (GLUT9) gene polymorphisms and gout susceptibility: an updated meta-analysis. Rheumatol Int. 2016; 36(8):1157-65. DOI: 10.1007/s00296-016-3503-6. View

12.

Thakkinstian A, McElduff P, DEste C, Duffy D, Attia J . A method for meta-analysis of molecular association studies. Stat Med. 2004; 24(9):1291-306. DOI: 10.1002/sim.2010. View

13.

Matsuo H, Chiba T, Nagamori S, Nakayama A, Domoto H, Phetdee K . Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia. Am J Hum Genet. 2008; 83(6):744-51. PMC: 2668068. DOI: 10.1016/j.ajhg.2008.11.001. View

14.

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

15.

Nakayama A, Nakaoka H, Yamamoto K, Sakiyama M, Shaukat A, Toyoda Y . GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes. Ann Rheum Dis. 2016; 76(5):869-877. PMC: 5530361. DOI: 10.1136/annrheumdis-2016-209632. View

16.

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

17.

Mallamaci F, Testa A, Leonardis D, Tripepi R, Pisano A, Spoto B . A genetic marker of uric acid level, carotid atherosclerosis, and arterial stiffness: a family-based study. Am J Kidney Dis. 2014; 65(2):294-302. DOI: 10.1053/j.ajkd.2014.07.021. View

18.

Jiri M, Zhang L, Lan B, He N, Feng T, Liu K . Genetic variation in the ABCG2 gene is associated with gout risk in the Chinese Han population. Clin Rheumatol. 2015; 35(1):159-63. DOI: 10.1007/s10067-015-3105-9. View

19.

Nakayama A, Matsuo H, Nakaoka H, Nakamura T, Nakashima H, Takada Y . Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia progression than typical environmental risk factors. Sci Rep. 2014; 4:5227. PMC: 5381477. DOI: 10.1038/srep05227. View

20.

Tu H, Chung C, Ko A, Lee S, Lai H, Lee C . Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk. J Hum Genet. 2016; 61(9):803-10. DOI: 10.1038/jhg.2016.57. View