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Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk

Lookup NU author(s): Professor Nick ReynoldsORCiD, Dr Simon Meggitt


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Background: Polymorphisms in the serine protease inhibitor gene serine peptidase inhibitor Kazal type 5 (SPINK5) and the serine protease kallikrein-related peptidase 7 gene (KLK7) appear to confer risk to eczema in some cohorts, but these findings have not been widely replicated. These genes encode proteins thought to be involved in the regulation of posttranslation processing of filaggrin (FLG), the strongest identified genetic risk factor for eczema to date. Objectives: We sought to clarify the individual risk of eczema conferred by the SPINK5 polymorphism rs2303067 (Glu420Lys) and a previously described insertion in the 3′ untranslated region of KLK7 and to examine potential epistatic effects between these variants and FLG mutations. Methods: Initially, we examined the effects of these polymorphisms and FLG in 486 unrelated patients from a German family-based study, an additional 287 German patients, and 418 unrelated Irish/English patients with eczema (n for 3 genes studied = 1191 vs 4544 control subjects). We then additionally studied the SPINK5 polymorphism and FLG mutations in 1583 patients with eczema from the Avon Longitudinal Study of Parents and Children cohort (sample size for 2 genes studied = 2774 vs 10,607 control subjects). Results: No association was seen with the SPINK5 or KLK7 variants in the case-control analysis; however, a weaker effect was observed for the SPINK5 variant with maternal transmission in the family-based study. No interactions were seen between the polymorphisms in KLK7, SPINK5, and FLG. Conclusion: The SPINK5 420LysSer mutation confers a risk of eczema when maternally inherited but is not a major eczema risk factor. The KLK7 insertion appears to confer no risk of eczema. We found no interaction between the SPINK5 risk allele or the putative KLK7 risk allele and FLG mutations. © 2008 American Academy of Allergy, Asthma & Immunology.

Publication metadata

Author(s): Weidinger S, Baurecht H, Wagenpfeil S, Henderson J, Novak N, Sandilands A, Chen H, Rodriguez E, O'Regan GM, Watson R, Liao H, Zhao Y, Barker JNWN, Allen M, Reynolds N, Meggitt S, Northstone K, Smith GD, Strobl C, Stahl C, Kneib T, Klopp N, Bieber T, Behrendt H, Palmer CNA, Wichmann H-E, Ring J, Illig T, McLean WHI, Irvine AD

Publication type: Article

Publication status: Published

Journal: Journal of Allergy and Clinical Immunology

Year: 2008

Volume: 122

Issue: 3

Pages: 560-568.e4

ISSN (print): 0091-6749

ISSN (electronic): 1097-6825

Publisher: Mosby, Inc.


DOI: 10.1016/j.jaci.2008.05.050


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Funder referenceFunder name
British Skin Foundation/National Eczema Association
Department of Paediatric Dermatology. Our Lady's Childlen's Hospital, Dublin
The UK Medical Research Council
Chief Scientists Office of the Scottish Executive Generation Scotland Initiative
Dystrophic Epidermolysis Bullosa Research Association
German Ministry of Education and Research (BMBF)
University of Bristol
Wellcome Trust
G07003 14Medical Research Council
KKF-27/05University Hospital "Rechts der Isar." Technical University Munich
KKF-07/04University Hospital "Rechts der Isar." Technical University Munich
NUW-S31T05National Genome Research Network (NGFN)