Association between IL13 Polymorphisms and Psoriatic Arthritis Is Modified by Smoking

Abstract

Genetic and environmental factors influence the development of psoriasis (Ps) and psoriatic arthritis (PsA). Recently, we reported that three IL13 polymorphisms, rs1800925, rs20541, and rs848, on chromosome 5q31 conferred the risk for Ps. IL13 encodes IL-13, a Th2 cytokine, and rs1800925 and rs20541 confer risk of asthma. Further, smoking may increase the risk of developing Ps. We examined the association between IL13 polymorphisms, smoking, and PsA in two Ps sample sets genotyped for rs1800925, rs20541, and rs848. We found that the minor alleles (rs1800925*T, rs20541*A, and rs848*A) were significantly associated with protection from PsA versus controls, and that no association with Ps is seen when the PsA cases are excluded. This effect was strongest with rs1800925*T (odds ratio (OR) 0.40, P(allelic) 0.000067). The prevalence of PsA in cases with the rs1800925*CT or TT genotype is about half that of those with the CC genotype (15.5 vs 32.1%, P=0.0002). However, smoking appears to abrogate this effect (CT/TT/non-smoker, prevalence of PsA 13%, OR 0.20, P=0.0001; CT/TT/smoker, prevalence 38%, OR 0.88, P=0.74, CC/non-smoker, prevalence 42% (reference), CC/smoker prevalence 47%, OR 1.21, P=0.47). This study suggests that IL13 polymorphisms associate most strongly with PsA and that smoking may modulate this effect.

IL-37 Ameliorates the Inflammatory Process in Psoriasis by Suppressing Proinflammatory Cytokine Production

“…IL-6 impairs Treg regulation and enables cutaneous T cells to escape from Treg suppression (33), thereby contributing to the poor suppression of T EM cells by Tregs, tipping the balance in favor of pathogenic Th1 and Th17 cells over Tregs. IL-13, a Th2 cytokine, which was shown to confer a modest risk for psoriasis, was also inhibited in our research (34). S100A7, also called psoriasin, belongs to the pleiotropic S100 family of calciumbinding proteins and was identified as a protein upregulated in abnormally differentiated psoriatic keratinocytes (35).…”

Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis

“…IL13 gene polymorphisms influence this relationship. In a recent study, it was shown that the minor alleles (rs1800925*T, rs20541*A, and rs848*A) are associated with protection from PsA versus controls [98]. No association with psoriasis was seen when PsA cases were excluded.…”

“…No association with psoriasis was seen when PsA cases were excluded. Smoking appeared to abrogate this protective effect [98].…”

Correlation between IL-3 and IL-13 gene polymorphisms in Chinese patients and rheumatoid arthritis

“…Heinzmann et al (2003), on the other hand, found no correlation between the IL-13 variant Arg110Gln and juvenile idiopathic arthritis compared to the controls. Several studies have indicated that a polymorphism in the IL-13 gene (rs1800925 C/T) was strongly associated with psoriatic arthritis (PsA) (Duffin et al 2009;Bowes et al, 2011;Eder et al, 2011). Moreover, it has been proposed that similar pathogenic mechanisms may be shared among other autoimmune diseases.…”