Gene polymorphism in Netherton and common atopic disease.
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.
Walley
A J
AJ
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
Chavanas
S
S
Moffatt
M F
MF
Esnouf
R M
RM
Ubhi
B
B
Lawrence
R
R
Wong
K
K
Abecasis
G R
GR
Jones
E Y
EY
Harper
J I
JI
Hovnanian
A
A
Cookson
W O
WO
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*
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