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Tytuł pozycji:

Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

Tytuł :
Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.
Index Terms :
Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD14/genetics; CARD Signaling Adaptor Proteins/genetics; Child; Europe; Female; Genetic Predisposition to Disease/genetics; Genotype; Gout/genetics; Gout/immunology; Humans; Inflammasomes/genetics; Interleukin-1beta/genetics; Male; Middle Aged; Neoplasm Proteins/genetics; New Zealand; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Polynesia; Young Adult
info:eu-repo/semantics/article
article
Wydawca :
2015
Dodane szczegóły :
McKinney, C.
Stamp, L.K.
Dalbeth, N.
Topless, R.K.
Day, R.O.
Kannangara, D.R.
Williams, K.M.
Janssen, M.
Jansen, T.L.
Joosten, L.A.
Radstake, T.R.
Riches, P.L.
Tausche, A.K.
Lioté, F.
So, A.
Merriman, T.R.
Typ dokumentu :
Zasób elektroniczny
URL :
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_29D3998119385">http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_29D3998119385
Dostępność :
Open access content. Open access content
info:eu-repo/semantics/openAccess
Copying allowed only for non-profit organizations
https://serval.unil.ch/disclaimer
Pozostałe numery :
CHLSR oai:serval.unil.ch:BIB_29D399811938
1008927291
Źródło wspomagające :
UNIV DE LAUSANNE-LETTRES,HIST,SCI RELG
From OAIster®, provided by the OCLC Cooperative.
Numer akcesji :
edsoai.on1008927291
Zasób elektroniczny
INTRODUCTION: The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. METHODS: 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. RESULTS: Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P < 0.05) associations with gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. CONCLUSION: There is evidence for association of gout with functional variants in CARD8

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