Interactive effect of STAT6 and IL13gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study

Ali H Ziyab,Hongmei Zhang,Wilfried Karmaus,Syed Hasan Arshad,John W Holloway,Marsha Wills-Karp,Julian M Hopkin,Susan Ewart,Eric M Schauberger,Gwyneth A Davies

doi:10.1186/1471-2350-14-67

Abstract

BackgroundEczema is a prevalent skin disease that is mainly characterized by systemic deviation of immune response and defective epidermal barrier. Th2 cytokines, such as IL-13 and transcription factor STAT6 are key elements in the inflammatory response that characterize allergic disorders, including eczema. Previous genetic association studies showed inconsistent results for the association of single nucleotide polymorphisms (SNPs) with eczema. Our aim was to investigate whether SNPs in IL13 and STAT6 genes, which share a biological pathway, have an interactive effect on eczema risk.MethodsData from two independent population-based studies were analyzed, namely the Isle of Wight birth cohort study (IOW; n = 1,456) and for the purpose of replication the Swansea PAPA (Poblogaeth Asthma Prifysgol Abertawe; n = 1,445) cross-sectional study. Log-binomial regressions were applied to (i) account for the interaction between IL13 (rs20541) and STAT6 (rs1059513) polymorphisms and (ii) estimate the combined effect, in terms of risk ratios (RRs), of both risk factors on the risk of eczema.ResultsUnder a dominant genetic model, the interaction term [IL13 (rs20541) × STAT6 (rs1059513)] was statistically significant in both studies (IOW: adjusted Pinteraction = 0.046; PAPA: Pinteraction = 0.037). The assessment of the combined effect associated with having risk genotypes in both SNPs yielded a 1.52-fold increased risk of eczema in the IOW study (95% confidence interval (CI): 1.05 – 2.20; P = 0.028) and a 2.01-fold higher risk of eczema (95% CI: 1.29 – 3.12; P = 0.002) in the PAPA study population.ConclusionsOur study adds to the current knowledge of genetic susceptibility by demonstrating for the first time an interactive effect between SNPs in IL13 (rs20541) and STAT6 (rs1059513) on the occurrence of eczema in two independent samples. Findings of this report further support the emerging evidence that points toward the existence of genetic effects that occur via complex networks involving gene-gene interactions (epistasis).

Highlights

Eczema is a prevalent skin disease that is mainly characterized by systemic deviation of immune response and defective epidermal barrier
Genotype frequencies of interleukin 13 (IL13) and Signal transducer and activator of transcription 6 (STAT6) polymorphisms were concordant with HardyWeinberg equilibrium
The current study investigated the association of single nucleotide polymorphism (SNP) in IL13 and STAT6 genes separately and jointly on the risk for eczema in two independent population-based studies

Summary

Introduction

Eczema is a prevalent skin disease that is mainly characterized by systemic deviation of immune response and defective epidermal barrier. Th2 cytokines, such as IL-13 and transcription factor STAT6 are key elements in the inflammatory response that characterize allergic disorders, including eczema. Eczema is an inflammatory skin disorder that is characterized by disrupted epidermal barrier function, immunoglobulin E (IgE)-. Chromosome 5q31-33 harbors genes, including interleukin 4 (IL4) and interleukin 13 (IL13), that encode Th2 cytokines, which are involved in the regulation of IgE synthesis and manifestation of allergic disorders [1,2,9,10]. Altered STAT6 activation may contribute to the major hallmarks of eczema: (i) allergic sensitization and (ii) impaired epidermal barrier

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