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Gene polymorphism in Netherton and common atopic disease

Abstract

Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions1, including the chromosome 5q31 cytokine cluster2,3,4. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment5. The gene underlying Netherton disease (SPINK5)6 encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus6,7. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420→Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses.

Table 1 Single-nucleotide polymorphisms in SPINK5

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Figure 1: Amino-acid sequence of the LEKTI protein, modified from previous description7.

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Acknowledgements

We are grateful to L. Cardon and to the reviewers for advice on the statistical analysis of data. Families with AD were recruited with the help of R. Coleman, R. Trembath and H. Cox. Serum IgE measurements were carried out by J.A. Faux. The study was funded by the National Asthma Campaign, the Wellcome Trust and the Medical Research Council. E.Y. Jones is funded by the Royal Society.

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Correspondence to William O.C.M. Cookson.

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Walley, A., Chavanas, S., Moffatt, M. et al. Gene polymorphism in Netherton and common atopic disease. Nat Genet 29, 175–178 (2001). https://doi.org/10.1038/ng728

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