Association between novel GM-CSF gene polymorphisms and the frequency and severity of atopic dermatitis

Background: Genetic factors are known to be important in determining an individual's predisposition to atopic dermatitis. The specific genes that are clinically important in this process are still largely unknown. Objective: Because dendritic cells initiate immune responses and thus are critical to the priming of an individual to potential allergens, we hypothesized that genetic factors controlling the activity of these cells determine an individual's propensity to atopic dermatitis. Methods: We studied known functional polymorphisms of the IL-1beta and TNF-alpha genes and describe novel polymorphisms of the GM-CSF gene in 113 children with atopic dermatitis and 114 controls. All 3 factors are known to be important modulators of the function of skin Langerhans' (dendritic) cells. Results: The inheritance of a homozygous GM-CSF -677*C/C genotype was associated with complete absence of severe atopic dermatitis within this cohort of children (P < .001). Furthermore, the odds ratio of having atopic dermatitis in children who were not of this genotype was 7.5 (2.2-25). Conclusion: The GM-CSF genotype is an important genetic marker predicting an individual's predisposition to atopic dermatitis.