Identifying genes predisposing to atopic eczema.
Forrest S., Dunn K., Elliott K., Fitzpatrick E., Fullerton J., McCarthy M., Brown J., Hill D., Williamson R.
BACKGROUND: Genetic and environmental factors are known to play a role in the development of atopic diseases, such as asthma, eczema, and rhinitis. However, the atopy gene (or genes) has yet to be defined. Studies of familial asthma have identified several regions that may contain genes predisposing to atopy, but the data for candidate regions do not show agreement, which may be due to heterogeneity, ascertainment bias, or stochastic factors. Factors such as an early age of onset, a positive family history, and a clearly defined phenotype favor a genetic origin and improve the chance of identifying genes that predispose to atopy. OBJECTIVE: We sought to define genes that predispose to the development of atopic eczema. METHODS: We have studied nuclear families with multiple cases of early-onset atopic eczema for involvement of the candidate regions on chromosomes 5q31 (IL gene cluster), 11q13 (high-affinity FCepsilon receptor), 14q11.2 (mast cell chymase), and 16p12 (IL-4 receptor alpha-chain, IL4RA gene). RESULTS: Using a recessive model, we find a maximum parametric log of the odds of linkage score of 2. 25 and nonparametric score of 2.54 (P =.006) for a region on chromosome 5q31, which we postulate contains a gene predisposing to atopic eczema, but lack of support for linkage to 11q13. Transmission disequilibrium tests do not support an association with candidate polymorphisms in the mast cell chymase and IL4RA genes. CONCLUSION: We have identified a clinically homogeneous cohort of patients with atopic eczema to identify genetic factors predisposing to the development of atopy. We postulate that there are certain loci that predispose to atopy in general and other loci that determine which of the atopic phenotypes is expressed.