Variants in the vitamin D receptor gene and asthma

Abstract

Background: Early lifetime exposure to dietary or supplementary vitamin D has been predicted to be a risk factor for later allergy. Twin studies suggest that response to vitamin D exposure might be influenced by genetic factors. As these effects are primarily mediated through the vitamin D receptor (VDR), single base variants in this gene may be risk factors for asthma or allergy.

Results: 951 individuals from 224 pedigrees with at least 2 asthmatic children were analyzed for 13 SNPs in the VDR. There was no preferential transmission to children with asthma. In their unaffected sibs, however, one allele in the 5' region was 0.5-fold undertransmitted (p = 0.049), while two other alleles in the 3' terminal region were 2-fold over-transmitted (p = 0.013 and 0.018). An association was also seen with bronchial hyperreactivity against methacholine and with specific immunoglobulin E serum levels.

Conclusion: The transmission disequilibrium in unaffected sibs of otherwise multiple-affected families seem to be a powerful statistical test. A preferential transmission of vitamin D receptor variants to children with asthma could not be confirmed but raises the possibility of a protective effect for unaffected children.

Figure 1

Structure of the vitamin D receptor [40, 41]. Upper: LD blocks in Caucasians [14] where blocks "C" and "A" extend to both sides. In Africans block "C" is split into 3 parts, "C1", "C2" and "C3". Middle: Exon structure including several SNP variants examined in about 100 disease-association studies. Lower: Aligned protein domains, DNA binding, hinge and ligand binding region including phosphorylation sites.

Figure 2

Excess transmission of VDR-SNPs in asthma families. Blue bars indicate transmission to affected children, grey bars transmission to unaffected children.

Figure 3

Age distribution in children with, blue box (left), and without asthma, grey box (right).