Evidence for a genetic interaction in allergy-related responsiveness to vitamin D deficiency.
BACKGROUND
The hormonal form of vitamin D affects both adaptive and innate immune functions involved in the development of allergies. Certain genotypes have been seen to alter the association between vitamin D deficiency (VDD) and the risk of food sensitization in children.


METHODS
We examined 27 functional single nucleotide polymorphisms (SNPs) in/near selected candidate genes for association with total immunoglobulin E (IgE) and effect modification by 25-hydroxyvitamin D in the 1958 British birth cohort (aged 45 years, n = 4921). A cut-off value of 50 nmol/L was used to define VDD.


RESULTS
Four SNPs (in FCER1A, IL13, and CYP24A1) and three SNPs (in IL4 and CYP24A1) were associated with total IgE and specific IgE, respectively, after correction for multiple testing. As in a previous study, MS4A2 (rs512555, P(interaction) = 0.04) and IL4 (rs2243250, P(interaction) = 0.02), and their composite score (P(interaction) = 0.009) modified the association between VDD and allergy-related outcome. Vitamin D deficiency was associated with higher total IgE only in the carriers of the 'C' allele (IL4), which is present in 86% of white Europeans, while only 26% of Chinese and <20% of some African populations are carriers.


CONCLUSIONS
Our study on white European adults was consistent with a previous study on children from largely non-white ethnic groups, suggesting that IL4 and MS4A2 genotypes modify the association between VDD and allergy risk. The risk allele in IL4 is present in nearly 90% of white Europeans, while less than a quarter are carriers in some other populations, highlighting the need to consider possible ethnic differences in allergy-related responsiveness to VDD.
Centre for Paediatric Epidemiology and Biostatistics and MRC Centre for the Epidemiology of Child Health, UCL Institute of Child Health, London, UK.
K S
KS
Vimaleswaran
A
A
Cavadino
E
E
Hyppönen
D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017455:Receptors, IgE / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000235:genetics* / Q000276:immunology*; D065668:Vitamin D3 24-Hydroxylase
C502447:MS4A2 protein, human; D017455:Receptors, IgE; D014807:Vitamin D; D015847:Interleukin-4; D007073:Immunoglobulin E; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase