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).


CONCLUSIONS
The GM-CSF genotype is an important genetic marker predicting an individual's predisposition to atopic dermatitis.
D000293:Adolescent; D001483:Base Sequence; D016022:Case-Control Studies; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D005819:Genetic Markers; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA