title: 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 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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Walley
authors.forename: S
authors.initials: S
authors.lastname: Chavanas
authors.forename: M F
authors.initials: MF
authors.lastname: Moffatt
authors.forename: R M
authors.initials: RM
authors.lastname: Esnouf
authors.forename: B
authors.initials: B
authors.lastname: Ubhi
authors.forename: R
authors.initials: R
authors.lastname: Lawrence
authors.forename: K
authors.initials: K
authors.lastname: Wong
authors.forename: G R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: E Y
authors.initials: EY
authors.lastname: Jones
authors.forename: J I
authors.initials: JI
authors.lastname: Harper
authors.forename: A
authors.initials: A
authors.lastname: Hovnanian
authors.forename: W O
authors.initials: WO
authors.lastname: Cookson
mesh_terms: D000595:Amino Acid Sequence; D001249:Asthma / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins; D017931:DNA Primers; D003876:Dermatitis, Atopic / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D053491:Proteinase Inhibitory Proteins, Secretory; D017386:Sequence Homology, Amino Acid; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors