Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout.
Détails
Télécharger: 32164793_BIB_537FBB6F9F66.pdf (600.99 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_537FBB6F9F66
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout.
Périodique
Arthritis research & therapy
ISSN
1478-6362 (Electronic)
ISSN-L
1478-6354
Statut éditorial
Publié
Date de publication
12/03/2020
Peer-reviewed
Oui
Volume
22
Numéro
1
Pages
45
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
The ABCG2 Q141K (rs2231142) and rs10011796 variants associate with hyperuricaemia (HU). The effect size of ABCG2 rs2231142 on urate is ~ 60% that of SLC2A9, yet the effect size on gout is greater. We tested the hypothesis that ABCG2 plays a role in the progression from HU to gout by testing for association of ABCG2 rs2231142 and rs10011796 with gout using HU controls.
We analysed 1699 European gout cases and 14,350 normouricemic (NU) and HU controls, and 912 New Zealand (NZ) Polynesian (divided into Eastern and Western Polynesian) gout cases and 696 controls. Association testing was performed using logistic and linear regression with multivariate adjusting for confounding variables.
In Europeans and Polynesians, the ABCG2 141K (T) allele was associated with gout using HU controls (OR = 1.85, P = 3.8E <sup>- 21</sup> and OR <sub>meta</sub> = 1.85, P = 1.3E <sup>- 03</sup> , respectively). There was evidence for an effect of 141K in determining HU in European (OR = 1.56, P = 1.7E <sup>- 18</sup> ) but not in Polynesian (OR <sub>meta</sub> = 1.49, P = 0.057). For SLC2A9 rs11942223, the T allele associated with gout in the presence of HU in European (OR = 1.37, P = 4.7E <sup>- 06</sup> ), however significantly weaker than ABCG2 rs2231142 141K (P <sub>Het</sub> = 0.0023). In Western Polynesian and European, there was epistatic interaction between ABCG2 rs2231142 and rs10011796. Combining the presence of the 141K allele with the rs10011796 CC-genotype increased gout risk, in the presence of HU, 21.5-fold in Western Polynesian (P = 0.009) and 2.6-fold in European (P = 9.9E <sup>- 06</sup> ). The 141K allele of ABCG2 associated with increased gout flare frequency in Polynesian (P <sub>meta</sub> = 2.5E <sup>- 03</sup> ).
These data are consistent with a role for ABCG2 141K in gout in the presence of established HU.
We analysed 1699 European gout cases and 14,350 normouricemic (NU) and HU controls, and 912 New Zealand (NZ) Polynesian (divided into Eastern and Western Polynesian) gout cases and 696 controls. Association testing was performed using logistic and linear regression with multivariate adjusting for confounding variables.
In Europeans and Polynesians, the ABCG2 141K (T) allele was associated with gout using HU controls (OR = 1.85, P = 3.8E <sup>- 21</sup> and OR <sub>meta</sub> = 1.85, P = 1.3E <sup>- 03</sup> , respectively). There was evidence for an effect of 141K in determining HU in European (OR = 1.56, P = 1.7E <sup>- 18</sup> ) but not in Polynesian (OR <sub>meta</sub> = 1.49, P = 0.057). For SLC2A9 rs11942223, the T allele associated with gout in the presence of HU in European (OR = 1.37, P = 4.7E <sup>- 06</sup> ), however significantly weaker than ABCG2 rs2231142 141K (P <sub>Het</sub> = 0.0023). In Western Polynesian and European, there was epistatic interaction between ABCG2 rs2231142 and rs10011796. Combining the presence of the 141K allele with the rs10011796 CC-genotype increased gout risk, in the presence of HU, 21.5-fold in Western Polynesian (P = 0.009) and 2.6-fold in European (P = 9.9E <sup>- 06</sup> ). The 141K allele of ABCG2 associated with increased gout flare frequency in Polynesian (P <sub>meta</sub> = 2.5E <sup>- 03</sup> ).
These data are consistent with a role for ABCG2 141K in gout in the presence of established HU.
Mots-clé
ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics, Disease Progression, Epistasis, Genetic, Europe, Female, Gene Frequency, Genetic Pleiotropy/genetics, Genetic Predisposition to Disease/genetics, Genotype, Gout/blood, Gout/genetics, Humans, Hyperuricemia/blood, Hyperuricemia/genetics, Male, Native Hawaiian or Other Pacific Islander/genetics, Neoplasm Proteins/genetics, New Zealand, Polymorphism, Single Nucleotide, Uric Acid/blood, White People/genetics, ABCG2, Association, Gout, Hyperuricemia, Polymorphism, Urate
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/04/2020 18:41
Dernière modification de la notice
08/08/2024 6:33