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Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study

Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study
Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study
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) x 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.

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).
eczema, gene-gene interaction, epistasis, STAT6, IL13, genetic association Study
1471-2350
1-9
Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Davies, Gwyneth A.
842455c0-70d8-4ea7-a87f-004f55e4a1bc
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Hopkin, Julian M.
9ef25db9-a954-4288-a2bf-327009626a9b
Schauberger, Eric M.
55117bab-f3f6-4a47-b083-d1fee2647567
Wills-Karp, Marsha
a59ab80a-d165-4078-aa11-dc597774cbb8
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Davies, Gwyneth A.
842455c0-70d8-4ea7-a87f-004f55e4a1bc
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Hopkin, Julian M.
9ef25db9-a954-4288-a2bf-327009626a9b
Schauberger, Eric M.
55117bab-f3f6-4a47-b083-d1fee2647567
Wills-Karp, Marsha
a59ab80a-d165-4078-aa11-dc597774cbb8
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853

Ziyab, Ali H., Davies, Gwyneth A., Ewart, Susan, Hopkin, Julian M., Schauberger, Eric M., Wills-Karp, Marsha, Holloway, John W., Arshad, Syed, Zhang, Hongmei and Karmaus, Wilfried (2013) Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study. BMC Medical Genetics, 14 (67), 1-9. (doi:10.1186/1471-2350-14-67). (PMID:23815671)

Record type: Article

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) x 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.

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).

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Published date: 2 July 2013
Keywords: eczema, gene-gene interaction, epistasis, STAT6, IL13, genetic association Study
Organisations: Human Development & Health, Clinical & Experimental Sciences

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Local EPrints ID: 354226
URI: http://eprints.soton.ac.uk/id/eprint/354226
ISSN: 1471-2350
PURE UUID: 5233251b-1067-4db3-8cd1-64d671a39a62
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 04 Jul 2013 15:45
Last modified: 28 Oct 2023 01:42

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Contributors

Author: Ali H. Ziyab
Author: Gwyneth A. Davies
Author: Susan Ewart
Author: Julian M. Hopkin
Author: Eric M. Schauberger
Author: Marsha Wills-Karp
Author: Syed Arshad
Author: Hongmei Zhang
Author: Wilfried Karmaus

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