Evidence for association and linkage between atopy, airway hyper-responsiveness, and the beta subunit Glu237Gly variant of the high-affinity receptorfor immunoglobulin E in the French-Canadian population

Following detection of linkage between atopy and chromosome 11q13 markers, association between this disorder and variants of the beta subunit of the h igh-affinity receptor for immunoglobulin E (Fc epsilon RI-beta, a candidate gene for asthma-related conditions co-localizing within the same region) w as reported in Australian, British and Japanese populations. Investigations in several other ethnic groups failed to replicate these observations. Due to the complexity of defining intermediate phenotypes related to asthma, d etection of such associations may have been hampered by clinical misclassif ications. To assess whether the Fc epsilon RI-beta gene was involved in ato py and/or airway hyperresponsiveness (AHR) in the French-Canadian populatio n, we conducted a case-control study in 200 subjects using strict criteria for asthma and related conditions. The Ile181Leu and Glu237Gly Fc epsilon R I-beta sequence variants were tested exploiting two amplification refractor y mutation systems. No association was detected between atopy or AHR and th e Ile181Leu Fc epsilon RI-beta variant. However, a strong association was o bserved between atopy and the Glu237Gly Fc epsilon RI-beta variant (odds ra tio=12.25). Four large Eastern Quebec families (n=106 subjects) were also r ecruited to perform a genetic linkage study. We observed suggestive evidenc e of linkage between atopy and the Glu237Gly Fc epsilon RI-beta Variant (Z( max)=2.30). This study is the first to detect the presence of an associatio n between atopy and the Glu237Gly Fc epsilon RI-beta variant in French-Cana dians. Our data suggest that a susceptibility locus for atopy is located on chromosome 11q13 in this population.