Cox, Helen Elizabeth; (1999) A clinical and genetic study of atopic dermatitis. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Atopic dermatitis is a chronic inflammatory skin disorder, sharing many pathogenic features with allergic asthma and rhinitis. It is a complex multifactorial disease, in which the underlying defect is still to be identified. 62 nuclear families (panel A) were recruited through a proband with active atopic dermatitis. The clinical genetics was defined and relevant genes predisposing to atopic dermatitis identified, using a candidate gene approach. Positive findings were tested in a second panel of 95 families (panel B). Polymorphisms within the beta chain of the high affinity IgE receptor gene (FcϵRI-β) on chromosome 11q were found to strongly associate with atopic dermatitis when maternally inherited. Using the transmission disequilibrium test, significant sharing of maternal alleles was found with allele 2 of RsaI intron 2, (FcϵRI-β Rsal_in2*2) (p=0.0022) and allele 1 of Rsal exon 7 (FcϵRI-β Rsal_ex7*l) (p=0.0036) and atopic dermatitis. These findings were replicated in panel B. The combined significance of the association of atopic dermatitis to Rsal polymorphisms was p=0.0002 (Rsal_in2*2) and p=0.00034 (Rsal_ex7*l). The polymorphisms also showed association with asthma; p=0.0068 (Rsal_in2*2) and p=0.0018 (Rsal_ex7*l). Analysis of a single polymorphism within the tumour necrosis factor (TNF) locus (LT-α Ncol) on chromosome 6, showed weak association to atopic dermatitis (p=0.032) and asthma (p=0.024). Atopic dermatitis failed however to associate significantly with a polymorphism within the promoter region of interleukin 4 on chromosome 5q. This study demonstrates genetic similarities underlying the development of atopic dermatitis and asthma. Both FcϵRI-β and TNF were identified as potential candidate genes. Furthermore, supportive evidence for a maternal effect was demonstrated.

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