Vitamin D deficiency linked to genetic polymorphisms

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By Katherine Harmon

At least half of adults in developed countries have deficient levels of vitamin D, and low levels of this vitamin have been linked to bone fragility, cancer, heart disease and immune system problems. Variable levels of vitamin D, which is a by-product of a chemical reaction that occurs when UV light hits the skin and can be found in some fatty fish, across populations has largely been thought to be a simple matter of exposure: failure to get enough sun, eat fatty fish or take supplements would result in deficiency.

Previous research has suggested that vitamin D levels were inherited, in part, but a new study of 33,996 people has found three specific genetic variants that seem to correlate with a person's levels of vitamin D.

Researchers ran a genome-wide association assay of 16,125 people from five centers in the U.S., Canada and Europe and found that three genetic polymorphisms were associated with varying levels of 25-hydroxyvitamin D, a biomarker used to test for levels of the vitamin itself. The researchers, led by Thomas Wang, of the Division of Cardiology in the Department of Medicine at Massachusetts General Hospital, also ran the same tests on another two batches of five cohorts each and found that the results replicated.

"The presence of harmful alleles at the three confirmed loci more than doubled the risk of vitamin D insufficiency," the researchers noted in their study, published online June 9 in The Lancet.

The genes in question (DHCR7/NADSYN1, CYP2R1 and GC) were involved in cholesterol synthesis, hydroxylation and vitamin D transport, respectively.

These findings were somewhat "unexpected," especially that none of the genes were linked to skin pigmentation or any of the major diseases implicated in vitamin D deficiency, Roger Bouillon, of the Clinic and Laboratory of Experimental Medicine and Endocrinology at Katholieke Universiteit Leuven in Belgium, noted in a commentary that appeared in the same issue of The Lancet. The new findings "only partly explain the wide variability of vitamin D status," he concluded.

The authors of the study agreed that the issue requires further study to shed light on the biological basis of the so-called sunshine vitamin. "Whether genetic predisposition modifies response to sun exposure or dietary supplementation warrants further study," the researchers wrote. "These variants might provide useful genetic approaches to investigate the role of vitamin D insufficiency in several chronic diseases."

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