Identifying genes predisposing to atopic eczema

Background: Genetic and environmental factors are known to play a role in t he development of atopic diseases such as asthma, eczema, and rhinitis, How ever, 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 ma y be due to heterogeneity, ascertainment bias, or stochastic factors. Facto rs 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 identify ing 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-onse t atopic eczema for involvement of the candidate regions on chromosomes 5q3 1 (IL gene cluster), 11q13 (high-affinity FC epsilon receptor), 14q11.2 (ma st cell chymase), and 16p12 (IL-4 receptor alpha-chain, IL4RA gene). Results: Using a recessive model, we find a maximum parametric log of the o dds 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 predisposi ng to atopic eczema, but lack of support for linkage to 11q13. Transmission disequilibrium tests do not support an association with candidate polymorp hisms 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 developm ent of atopy. We postulate that there are certain loci that predispose to a topy in general and other loci that determine which of the atopic phenotype s is expressed.