Association between IL13 Polymorphisms and Psoriatic Arthritis Is Modified by Smoking

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.