The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets

PloS One
Humaira RasheedTony R Merriman

Abstract

Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the r...Continue Reading

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Citations

Dec 9, 2016·Expert Opinion on Drug Metabolism & Toxicology·Richard O DayGarry G Graham
Sep 30, 2017·Nature Reviews. Rheumatology·Alexander K So, Fabio Martinon
Dec 24, 2018·Current Opinion in Rheumatology·Vicky TaiNicola Dalbeth
May 10, 2018·Nature Reviews. Rheumatology·Tanya J MajorTony R Merriman
Feb 10, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maria Antonelli, Irving Kushner
Aug 19, 2017·BMC Medicine·Robert Terkeltaub
Jun 2, 2017·BMC Medicine·Nicola DalbethTony R Merriman
Jun 20, 2020·Nucleosides, Nucleotides & Nucleic Acids·Rosa J Torres
Jun 1, 2021·Expert Review of Clinical Immunology·Paola GalozziFrancesca Oliviero
Aug 15, 2021·International Journal of Rheumatic Diseases·Denise Clavijo-CornejoMarwin Gutierrez

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