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 regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. 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.

Original publication

DOI

10.1038/ng728

Type

Journal article

Journal

Nature genetics

Publication Date

10/2001

Volume

29

Pages

175 - 178

Addresses

Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.

Keywords

Humans, Asthma, Dermatitis, Atopic, Carrier Proteins, DNA Primers, Serine Proteinase Inhibitors, Amino Acid Sequence, Base Sequence, Sequence Homology, Amino Acid, Polymorphism, Single Nucleotide, Molecular Sequence Data, Proteinase Inhibitory Proteins, Secretory