Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women.
Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02; OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001; OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy; i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies.
Applied Genomics Research Group, McClay Research Centre, The Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK.
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Suppiah
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Rooney
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Vandenbroeck
D001120:Arginine / Q000235:genetics; D001171:Arthritis, Juvenile / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D003596:Cytosine; D005260:Female; D005787:Gene Frequency; D005973:Glutamine / Q000235:genetics; D006720:Homozygote; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D007494:Ireland; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D012307:Risk Factors; D013941:Thymine
D019948:Receptors, Interleukin-4; D005973:Glutamine; D015847:Interleukin-4; D003596:Cytosine; D001120:Arginine; D013941:Thymine