Common genetic determinants of vitamin D insufficiency

January 01, 0001

Common genetic determinants of vitamin D insufficiency

Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. The researchers aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. They undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L.

Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts. Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L or lower than 50 nmol/L compared with those in the lowest quartile.

The researchers concluded: "Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency."

An interesting examples of the fine-tuning that genomics allows.

For the full abstract, click here.

The Lancet published online June 2010 © Elsevier Ltd 2010
Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Thomas J Wang, Feng Zhang and J Brent Richards. Correspondence to Thomas Wang: [email protected]

Category: T. Endocrine/Metabolic/Nutritional. Keywords: genetic, determinants, vitamin D, insufficiency, genome-wide association study, journal watch.
Synopsis edited by Dr Stephen Wilkinson, Melbourne, Australia. Posted on Global Family Doctor 9 July 2010

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.