Association of NLRP3 and CARD8 genetic polymorphisms with juvenile idiopathic arthritis in a Taiwanese population
Journal
Scandinavian Journal of Rheumatology
Journal Volume
43
Journal Issue
2
Pages
146-152
Date Issued
2014
Author(s)
Abstract
Objectives: An elevated interleukin (IL)-1β response in peripheral blood mononuclear cells (PBMCs) has been observed in systemic juvenile idiopathic arthritis (sJIA), suggesting a role for inflammasomes in the pathogenesis of JIA. We aimed to determine whether genetic polymorphisms of the NLRP3 inflammasome components confer risk for oligoarticular and polyarticular JIA in a Taiwanese population. Method: A total of 118 JIA patients and 103 healthy controls were genotyped for rs4353135 OR2B11/NLRP3 and rs2043211 CARD8 polymorphisms. Clinical laboratory data and serum IL-1β of JIA patients were evaluated by medical chart review and enzyme-linked immunosorbent assay (ELISA), respectively. The production of IL-17 in lymphocytes of different genotype carriers was measured using flow cytometry. Results: The variant rs4353135 G allele carrier conferred increased risk for oligoarticular and polyarticular JIA. The G allele was also found to be associated with higher levels of clinical inflammatory markers. Moreover, G variant carriers enhanced the lymphocyte IL-17 response. The G/G genotype further increased the need for treatment with the tumour necrosis factor (TNF) inhibitor etanercept. Conclusions: Our data indicate that the rs4353135 OR2B11/NLRP3 polymorphism might be functional in, and could contribute to, the pathophysiology of oligoarticular and polyarticular JIA in a Taiwanese population. ? 2014 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation.
SDGs
Other Subjects
adaptor protein; caspase recruitment domain protein 8; cryopyrin; DNA; inflammasome; interleukin 17; interleukin 1beta; unclassified drug; adolescent; article; case control study; child; Chinese; chronic disease; controlled study; cytokine production; enzyme linked immunosorbent assay; ethnic group; female; flow cytometry; genetic polymorphism; genotype; human; immune system; juvenile rheumatoid arthritis; major clinical study; male; onset age; pathophysiology; peripheral blood mononuclear cell; polymerase chain reaction; priority journal; single nucleotide polymorphism; Taiwan; Adolescent; Alleles; Arthritis, Juvenile; CARD Signaling Adaptor Proteins; Carrier Proteins; Case-Control Studies; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Genotype; Homozygote; Humans; Immunoglobulin G; Inflammasomes; Interleukin-17; Interleukin-1beta; Male; Neoplasm Proteins; Polymorphism, Single Nucleotide; Receptors, Tumor Necrosis Factor; Taiwan; Tumor Necrosis Factor-alpha
Publisher
Informa Healthcare
Type
journal article