Auteur Topic: 4 genetische varianten > associatie met lage vitamine D-waarde  (gelezen 1784 keer)


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4 genetische varianten > associatie met lage vitamine D-waarde
« Gepost op: juni 11, 2010, 14:07:46 »
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(Maar er zijn al veel meer berichten hierover te lezen:
Scientists Find Gene Links to Vitamin D Deficiency
Vitamin D insufficiency? EU-funded researchers say genes matter,
Genes May Be a Source of Vitamin D Deficiency
Four gene variants that affect vitamin D levels identified)

Common genetic determinants of vitamin D insufficiency:
a genome-wide association study

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.
We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency.

We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33996 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.
We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis.
Genotype scores were constructed for confirmed variants.

Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts:
4p12 (overall p=1𢗁0−109 for rs2282679, in GC); 11q12 (p=2🹡0−27 for rs12785878, near DHCR7); and 11p15 (p=3𠠹0−20 for rs10741657, near CYP2R1).
Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6🥵0−10 for rs6013897).

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 247, 95% CI 220𦌯8, p=2𠠹0−48) or lower than 50 nmol/L (192, 170𦌩6, p=1🥵0−26) compared with those in the lowest quartile.

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.

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Four genetic variants associated with low levels of vitamin D

June 9, 2010 | Lisa Nainggolan
Boston, MA -
A new genomewide association study (GWAS) has identified four genetic variants at different loci that appear to be associated with vitamin-D insufficiency in white people [1]. Dr Thomas J Wang (Massachusetts General Hospital, Boston, MA) and colleagues report their findings online June 9, 2010 in the Lancet.

"All the variants were near genes suspected to be involved in vitamin-D metabolism, so they were quite plausible," Wang, who is a cardiologist, told heartwire. Asked if there was any direct relevance of these findings to cardiovascular disease, Wang replied: "Obviously, as a cardiologist I'm interested overall in the question of vitamin-D deficiency and whether that impacts on heart disease, but this study didn't directly address that. This was a first step.

"There is a further step that one might envision where one might like to look at whether these genetic variants are ultimately related to cardiovascular risk," he added. "This might provide some clues as to whether there is a cause-and-effect association between vitamin-D status and CVD."

But it is "probably worth emphasizing that further work is not trivial; it will require very large samples. The genetic effects aren't very large, and there are many environmental effects as well," Wang says. "To relate variants to the more interesting clinical traits requires very large studies and very large collaborations." He says this is "certainly going to happen, but it may take some time to marshal those efforts."

In an accompanying editorial [2], Dr Roger Bouillon (Catholic University, Leuven, Belgium) says the results of Wang et al "only partly explain the wide variability of vitamin-D status, and whether these genetically based variants modify the health outcomes in vitamin-D deficiency is not known."

In the meantime, Wang says the large randomized Vitamin D and Omega-3 Trial (VITAL), sponsored by National Institutes of Health, looking at whether 2000-IU vitamin-D and/or omega-3 fatty-acid supplementation can reduce the risk of developing heart disease, stroke, or cancer in 20 000 men and women will, "in a more conventional manner, directly address the question of whether vitamin-D supplementation lowers CV risk." Another study also addressing this issue, the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) study, is looking at rosiglitazone vs pioglitazone in people with type 2 diabetes at risk of heart disease but also has an arm looking at vitamin D vs placebo. However, the fate of this trial remains unclear; because of the recent US Senate inquiry into rosiglitazone, among other things, there have been calls for TIDE to be halted.

Groeten, Ine