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The association between genetic polymorphisms in ABCG2 and SLC2A9 and urate: an updated systematic review and meta-analysis.
BMC Med Genet. 2020 Oct 21; 21(1):210.BM

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 .

Links

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Authors+Show Affiliations

Lukkunaprasit T
Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok, 10400, Thailand. Department of Pharmacology, College of Pharmacy, Rangsit University, Pathum Thani, Thailand.
Rattanasiri S
Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok, 10400, Thailand. sasivimol.rat@mahidol.edu.
Turongkaravee S
Social and Administrative Pharmacy Excellence Research (SAPER) Unit, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Suvannang N
Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok, 10400, Thailand.
Ingsathit A
Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok, 10400, Thailand.
Attia J
Centre for Clincial Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, and Hunter Medical Research Institute, Newcastle, NSW, Australia.
Thakkinstian A
Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Rd., Ratchathewi, Bangkok, 10400, Thailand.

MeSH

ATP Binding Cassette Transporter, Subfamily G, Member 2AllelesAsian PeopleFemaleGene ExpressionGene FrequencyGenotypeGlucose Transport Proteins, FacilitativeGoutHumansHyperuricemiaMaleNeoplasm ProteinsOdds RatioPolymorphism, Single NucleotideUric AcidWhite People

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

33087043

Citation

Lukkunaprasit, Thitiya, et al. "The Association Between Genetic Polymorphisms in ABCG2 and SLC2A9 and Urate: an Updated Systematic Review and Meta-analysis." BMC Medical Genetics, vol. 21, no. 1, 2020, p. 210.
Lukkunaprasit T, Rattanasiri S, Turongkaravee S, et al. The association between genetic polymorphisms in ABCG2 and SLC2A9 and urate: an updated systematic review and meta-analysis. BMC Med Genet. 2020;21(1):210.
Lukkunaprasit, T., Rattanasiri, S., Turongkaravee, S., Suvannang, N., Ingsathit, A., Attia, J., & Thakkinstian, A. (2020). The association between genetic polymorphisms in ABCG2 and SLC2A9 and urate: an updated systematic review and meta-analysis. BMC Medical Genetics, 21(1), 210. https://doi.org/10.1186/s12881-020-01147-2
Lukkunaprasit T, et al. The Association Between Genetic Polymorphisms in ABCG2 and SLC2A9 and Urate: an Updated Systematic Review and Meta-analysis. BMC Med Genet. 2020 Oct 21;21(1):210. PubMed PMID: 33087043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The association between genetic polymorphisms in ABCG2 and SLC2A9 and urate: an updated systematic review and meta-analysis. AU - Lukkunaprasit,Thitiya, AU - Rattanasiri,Sasivimol, AU - Turongkaravee,Saowalak, AU - Suvannang,Naravut, AU - Ingsathit,Atiporn, AU - Attia,John, AU - Thakkinstian,Ammarin, Y1 - 2020/10/21/ PY - 2020/8/16/received PY - 2020/10/13/accepted PY - 2020/10/22/entrez PY - 2020/10/23/pubmed PY - 2021/1/9/medline KW - ABCG2 KW - Gout KW - Hyperuricemia KW - Meta-analysis KW - SLC2A9 KW - Single nucleotide polymorphism KW - Urate SP - 210 EP - 210 JF - BMC medical genetics JO - BMC Med Genet VL - 21 IS - 1 N2 - 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 . SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/33087043/The_association_between_genetic_polymorphisms_in_ABCG2_and_SLC2A9_and_urate:_an_updated_systematic_review_and_meta_analysis_ DB - PRIME DP - Unbound Medicine ER -