@article{c100751608c74909b30178a1f6dfb09a,
title = "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",
abstract = "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.",
keywords = "Eczema, atopy, epistasis, skin barrier, stratum corneum",
author = "Stephan Weidinger and Hansj{\"o}rg Baurecht and Stefan Wagenpfeil and John Henderson and Natalija Novak and Aileen Sandilands and Huijia Chen and Elke Rodriguez and O'Regan, {Grainne M.} and Rosemarie Watson and Haihui Liao and Yiwei Zhao and Barker, {Jonathan N.W.N.} and Michael Allen and Nick Reynolds and Simon Meggitt and Kate Northstone and Smith, {George D.} and Carolin Strobl and Caroline Stahl and Thomas Kneib and Norman Klopp and Thomas Bieber and Heidrun Behrendt and Palmer, {Colin N.A.} and Wichmann, {H. Erich} and Johannes Ring and Thomas Illig and McLean, {W. H.Irwin} and Irvine, {Alan D.}",
note = "Funding Information: Disclosure of potential conflict of interest: N. Reynolds has served as an investigator in an investigator-initiated study for Stiefel, UK, and as an expert witness for Newcastle University on antipsoriatic therapy in research. J. Ring has received research support from Novartis, Schering-Plough, Fujisawa, GlaxoSmithKline, Bencard, Stallergenes, ALK-Abell{\'o}, Allergopharma, Pharmacia, DPC Biermann, Aventis, Almirall, Leo, Galderma, and Switch Biotech and has served as president of Allergopharma. A. D. Irvine has received funding from the Children's Medical and Research Foundation. The rest of the authors have declared that they have no conflict of interest. Funding Information: Supported by the German Ministry of Education and Research (BMBF) as part of the National Genome Research Network (NGFN) with grant NUW-S31T05. S. Weidinger and S. Wagenpfeil are supported by research grants KKF-07/04 and KKF-27/05 of the University Hospital “Rechts der Isar,” Technical University Munich. In addition, Dr Weidinger is supported by a grant from the “Wilhelm-Vaillant Stiftung.” The UK Medical Research Council, the Wellcome Trust, and the University of Bristol provide core support for Avon Longitudinal Study of Parents and Children. Additional funding was obtained from the Department of Paediatric Dermatology, Our Lady's Children's Hospital, Dublin, and by a grant from Tenovus (Tayside) to C.N.P. C.N.P. is supported by the Chief Scientists Office of the Scottish Executive Generation Scotland Initiative. The McLean laboratory is supported by grants from British Skin Foundation/National Eczema Association, the Pachyonychia Congenita Project, the Dystrophic Epidermolysis Bullosa Research Association, the Medical Research Council (reference no. G0700314), and anonymous donations from atopic families in the Tayside region of Scotland. ",
year = "2008",
month = sep,
doi = "10.1016/j.jaci.2008.05.050",
language = "English",
volume = "122",
pages = "560--568.e4",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Elsevier Inc.",
number = "3",
}