Analysis of the high affinity IgE receptor genes reveals epistatic effects of FCER1A variants on eczema risk

To cite this article: Mahachie John JM, Baurecht H, Rodriguez E, Naumann A, Wagenpfeil S, Klopp N, Mempel M, Novak N, Bieber T, Wichmann H-E, Ring J, Illig T, Cattaert T, Van Steen K, Weidinger S. Analysis of the high affinity IgEreceptor genes reveals epistatic effects of FCER1Avariants eczema risk. Allergy 2010; 65: 875–882. Abstract Background:  High levels of total and allergen-specific IgElevels are a key feature in allergic diseases. The high-affinity receptor for IgE, which is composed of one alpha ( FCER1A), one beta (FCER1B), and two gamma (FCER1G) subunits, represents the central receptor of IgE-induced reactions. In a genome-wide association scan, we recently identified associations between functional FCER1Avariants and total serum IgElevels. Previous studies had reported linkage and association of FCER1B variants with IgEand atopic traits. The FCER1G gene has not yet been investigated with regard to atopy. Filaggrin(FLG) is the strongest known risk gene for eczema, in particular the allergic subtype of eczema. Methods:  We investigated the association of FCER1A, FCER1B, and FCER1G variants with IgEin a large population-based cohort (n = 4261) and tested for epistatic effects using the model-based multifactor dimensionality reduction(MB-MDR) method. In addition, we investigated a potential interaction between FLG and FCER1Avariants in a large collection of eczema cases (n = 1018) and population controls. Results:  Three strongly correlated FCER1Apolymorphisms were significantly associated with total and specific IgElevels as well as allergic sensitization. No associations were seen for FCER1B and FCER1G. After adjustment for FLG effects, a significant epistatic effect of the FCER1Avariants rs10489854 and rs2511211 on eczema risk was detected. Conclusions:  These results suggest that FCER1Avariants by themselves and in combination influence IgElevels and act synergistically to influence eczema risk.