Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471

The influence of the SLC11A1 (formerly NRAMP1) gene on the association between BCG vaccination and atopy in children was studied in 179 children, BCG vaccinated in infancy, and 307 children without BCG vaccination, all 3 to 8 years of age and with atopic heredity. DNAs were genotyped for a functional repeat polymorphism (designated GT(n)) in the promoter of SLC11A1 and a linked microsatellite D2S1471. Associations between genotype, atopic symptoms and allergen-specific IgE-antibodies in relation to the BCG status of the children were assessed. Atopy in relation to SLC11A1 GT(n)-alleles was similarly distributed between the two groups. In BCG vaccinated children, genotype associations were observed for D2S1471 and atopy, with carriage of allele 5 conferring increased risk of atopy (odds ratio (OR) 2.6; 95% confidence interval (Cl) 1.3-5.5; P = 0.01), and particularly IgE responses to airborne allergens (OR = 4.3; 95% Cl 1.7-10.7, P = 0.002). No linkage disequilibrium was found between the SLC11A1 GT(n) repeat and the microsatellite D2S1471, and therefore no haplotype associations were observed for atopy in BCG- or non-BCG vaccinated children. Stratification by BCG vaccination unmasked a potential genetic risk factor for atopy in the region of the SLC11A1 locus, and point to the importance of genotype by environment interactions in determining disease susceptibility.