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 prot einases. Loci influencing atopy have been localized to a number of chromoso mal regions', including the chromosome 5q31 cytokine cluster(2-4). Netherto n disease is a rare recessive skin disorder in which atopy is a universal a ccompaniment(5). The gene underlying Netherton disease (SPINK5)(6) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epith elial and mucosal surfaces and in the thymus(6,7). We have identified six c oding polymorphisms in SPINK5 (Table 1) and found that a Glu420 --> Lys var iant shows significant association with atopy and AD in two independent pan els of families. Our results implicate a previously unrecognized pathway fo r the development of common allergic illnesses.