Vitamin D levels not tied to risks of asthma, dermatitis
Low levels of vitamin D due to genetic polymorphism is not associated with increased risks of immune-mediated diseases such as asthma and atopic dermatitis, nor is it linked to increased total serum immunoglobulin E (IgE), in contrast to previous observations from epidemiological studies.
“Our findings suggest that the previous epidemiological associations between vitamin D and atopic diseases could be due to confounding,” said lead author Despoina Manousaki from the Lady Davies Institute for Medical Research, McGill University in Montreal, Canada. “Efforts to increase vitamin D levels will probably not result in decreased risk of adult and paediatric asthma, atopic dermatitis, or elevated IgE levels.”
Four single-nucleotide polymorphisms (SNPs) known to be associated with reduced levels of serum vitamin D, measured in the form of 25-hydroxyvitamin D (25OHD) in the previous Canadian Multicentre Osteoporosis Study, were identified: rs12785878 near
DHCR7 (encoding for 7-dehydrocholesterol reductase), rs2282679 in GC (encoding for vitamin D binding protein), rs10741657 near
CYP2R1 (for cytochrome P450 2R1), and rs6013897 in CYP24A1 (for cytochrome P450 24A1).
All the genes were previously shown to modulate 25OHD levels through synthesis, transport, hydroxylation, and degradation. Therefore, having any of these SNPs represents a lifelong exposure to reduced levels of vitamin D.
Among the 33,996 participants analysed, none of the four SNPs were associated with asthma (including childhood asthma) or atopic dermatitis compared with normal alleles of the genes (p≥0.1 for all). Individuals who carried any of the SNPs also did not have higher IgE levels than those without the polymorphisms (p≥0.2 for all). [PLoS Med 2017;14:e1002294]
A Mendelian randomization analysis using a fixed-effects model showed that participants harbouring any of the four SNPs did not have increased risks of asthma (odds ratio [OR], 1.03; p=0.63), childhood asthma (OR, 0.95; p=0.76), atopic dermatitis (OR, 1.12; p=0.27), or elevated IgE levels (p=0.54).
These findings were further confirmed in sensitivity analyses after accounting for population stratification and pleiotropy, as well as the effects of independent pathways of vitamin D synthesis and metabolism.
“Although genetically lowered total 25OHD levels do not appear to be associated with increased risk of the studied atopic phenotypes, we have not assessed whether reduced lifelong 1,25-dihydroxyvitamin D [the active form of vitamin D] could influence these outcomes,” noted Manousaki and co-authors.
They also acknowledged that since the participants consisted of only Caucasian populations of European ancestry, more study is needed to ascertain if the findings also apply to other populations.
“Our previous findings suggest that low vitamin D levels increase risk for some inflammatory diseases like multiple sclerosis, but these effects do not translate to other inflammatory diseases like asthma and atopic dermatitis,” said study senior investigator Dr Brent Richards of McGill University.