Interleukin-4/interleukin-4 receptor gene polymorphisms in hand osteoarthritis

• Published in: Osteoarthritis and cartilage Vol. 18; no. 6; pp. 810 - 816
• Main Authors: Vargiolu, M, Silvestri, T, Bonora, E, Dolzani, P, Pulsatelli, L, Addimanda, O, Mancarella, L, Punzi, L, Fioravanti, A, Facchini, A, Romeo, G, Meliconi, R
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2010
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Association Study; Cytokines; Female; Gene Frequency; Gene Polymorphism; Genetic Predisposition to Disease; Genotype; Hand; Hand Osteoarthritis; Humans; IL-4 Receptor; Interleukin-4 - genetics; Male; Middle Aged; Osteoarthritis - genetics; Polymorphism, Single Nucleotide - genetics; Receptors, Interleukin-4 - genetics; Rheumatology; Gene Polymorphism; Hand Osteoarthritis; Cytokines; Association Study; IL-4 Receptor
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2010.02.005

Summary Objective IL-13/IL-4/IL-4R system has strong chondroprotective activity. We investigated polymorphisms in these genes as potential hand osteoarthritis (OA) susceptibility loci by performing a case–control association study. Methods Eighteen common single nucleotide polymorphisms (SNPs) (nine in IL-4R , five in IL-4 and four in IL-13 ) were genotyped in 403 patients (380 females) with hand OA and 322 healthy controls (308 females). Results Two SNPs (rs1805013 and rs1805015), mapping to the IL-4R gene, were associated with P -values of 0.0116 and 0.0305 respectively in the whole sample. As far as the non-erosive hand OA group ( n = 159) is concerned, the significance level of association of SNP rs1805013 is increased. After correction for multiple testing (correction for the 54 tests) the significance was not retained. None of the IL-13 SNPs analyzed showed association with hand OA. Some of the analyzed SNP within the IL-4 gene showed significant association with hand OA only when considering subgroups of patients. With respect to the CMC1 OA group, two SNPs in IL-4 (rs2243250 and rs2243274) showed association with a P -value of 0.027 and 0.018 respectively. None of these associations remained after correction for multiple testing. Conclusions The present study shows a trend to an association between non-erosive hand OA in Caucasian population and a genetic variant in the coding region of IL-4R gene. Our results, in keeping with previous data on hip OA, confirm the suggestion that IL-4 / IL-4R system plays a role in OA pathogenesis. Further confirmation studies on different populations are necessary.