GENETIC EPIDEMIOLOGY OF ATOPY AND THE HYGIENE HYPOTHESIS
McDonald, Merry-Lynn Noelle
Decreased exposure to microorganisms may be the reason the prevalence of allergic diseases has been increasing for the past several decades in westernized countries 1. This postulate, the hygiene hypothesis, was formulated by Strachan when he observed after following a large cohort of children for 23 years that being born late in the birth order and being from a large family were protective for allergic diseases'. More recent studies have demonstrated that the prevalence of atopic sensitization is lower in the children of farmers 3-6. Collectively, these studies appear to indicate that an appropriate microbial load is necessary to confer protection from allergic diseases. The Toll-Like Receptor 4 mutation (TLR4 D2990) is known to confer hypo-responsiveness to bacterial endotoxin in some individuals7,8. Individuals who carry this mutation may require additional bacterial challenge to switch to a non-allergic phenotype. Consequently, this thesis investigated the hypotheses that the TLR4 D2990 was a significant predictor of atopic status in Humboldt, SK family-based data and that the effect of parental history on allergic diseases was modified by the environmental covariates: family size, farming exposures, pets and smoking in addition to age and sex. Overall, 734 children participated from Humboldt, SK in the study representing a response rate of 79.1 %. The crude prevalence of atopy in this population of children was 30.4%. TLR4 D2990 was not associated with atopy in this population of children even though the power to detect such an association if it existed was high. Of the 734 children, 309 children had both parents participate in the study representing 111 non-farming and 68 farming families. Based on the variables; total number of siblings, parental smoking, pets, humidity, parental history of allergic diseases and parental atopy, farming families did not differ from non-farming families in this study. Children whose parents farmed, whose parents worked with livestock or whose parents had atopy were not at a decreased or an increased risk of being atopic in this study. The reduced model consisting of the variables age, sex and parental history of allergic disease was the most parsimonious for the outcome variable, atopy.