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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471
J S Alm1, C B Sanjeevi, E N Miller
1Department of Medicine, Unit of Clinical Allergy Research, Karolinska Hospital and Institutet, Stockholm, Sweden. Johan.Alm@sos.ki.se
Insights
The SLC11A1 gene may influence atopy risk in BCG-vaccinated children. Specific D2S1471 alleles increased atopy and IgE responses to allergens, highlighting gene-environment interactions in disease susceptibility.
Area of Science:
- Immunogenetics
- Pediatric Allergy
- Molecular Epidemiology
Background:
- Atopy, a predisposition to allergic diseases, is influenced by genetic and environmental factors.
- Bacille Calmette-Guérin (BCG) vaccination is known to modulate immune responses.
- The SLC11A1 gene (formerly NRAMP1) plays a role in innate immunity and has been investigated for its association with various diseases.
Purpose of the Study:
- To investigate the influence of the SLC11A1 gene on the association between BCG vaccination and atopy in children.
- To examine the relationship between SLC11A1 polymorphisms, BCG status, and the development of atopic symptoms and IgE responses.
Main Methods:
- Genotyping of 179 BCG-vaccinated and 307 unvaccinated children (3-8 years old) with atopic heredity for SLC11A1 promoter polymorphism (GTn) and linked microsatellite D2S1471.
- Assessment of associations between genotypes, atopic symptoms, and allergen-specific IgE levels in relation to BCG vaccination status.
- Analysis of linkage disequilibrium between SLC11A1 GTn and D2S1471.
Main Results:
- Atopy distribution was similar between BCG-vaccinated and unvaccinated groups concerning SLC11A1 GTn-alleles.
- In BCG-vaccinated children, D2S1471 genotype was associated with atopy (allele 5: OR 2.6) and IgE responses to airborne allergens (OR 4.3).
- No linkage disequilibrium was found between SLC11A1 GTn and D2S1471, precluding haplotype analysis.
Conclusions:
- BCG vaccination status can unmask genetic risk factors for atopy near the SLC11A1 locus.
- The findings suggest significant genotype by environment interactions in determining susceptibility to atopy.
- The D2S1471 marker, linked to SLC11A1, may represent a genetic risk factor for atopy in BCG-vaccinated children.
Abstract:
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 GTn) 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 GTn-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 (CI) 1.3-5.5; P = 0.01), and particularly IgE responses to airborne allergens (OR = 4.3; 95% CI 1.7-10.7; P = 0.002). No linkage disequilibrium was found between the SLC11A1 GTn 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.
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