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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2013

Open Access 01-12-2013 | Research article

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

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

Published in: BMC Medical Genetics | Issue 1/2013

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Abstract

Background

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. 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.

Methods

Data 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.

Results

Under a dominant genetic model, the interaction term [IL13 (rs20541) × STAT6 (rs1059513)] was statistically significant in both studies (IOW: adjusted P interaction = 0.046; PAPA: P interaction = 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.

Conclusions

Our 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).
Appendix
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Metadata
Title
Interactive effect of STAT6 and IL13gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study
Authors
Ali H Ziyab
Gwyneth A Davies
Susan Ewart
Julian M Hopkin
Eric M Schauberger
Marsha Wills-Karp
John W Holloway
Syed Hasan Arshad
Hongmei Zhang
Wilfried Karmaus
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2013
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-14-67

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