2010 June 21 Monday
Vitamin D Deficiency Due To Genetic Variants

If you are low in vitamin D it might be due to your genes.

An international research consortium has identified four common gene variants that are associated with blood levels of vitamin D and with an increased risk of vitamin D deficiency. The report from the SUNLIGHT consortium involving investigators from six countries will appear in The Lancet and is receiving early online release.

"We identified four common variants that contributed to the risk for vitamin D deficiency," says Thomas Wang, MD, of the Massachusetts General Hospital (MGH) Heart Center, a co-corresponding author of the Lancet report. "Individuals inheriting several of these risk-associated variants had more than twice the risk of vitamin D deficiency as was seen in those without these variants."

So the obvious question: What selective pressure produced genetic variants that lower blood vitamin D level? What was (and perhaps still is) the selective benefit of absorbing less vitamin D, breaking it down more rapidly, or synthesizing less of it in the skin? Did people who work outside (i.e. most humans for most of human history) produce too much vitamin D?

Four common genetic variants contribute to higher risk of vitamin D deficiency.

The SUNLIGHT (Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits) Consortium involved a research team from the U.S., U.K., Canada, Netherlands, Sweden and Finland who pooled data from 15 epidemiologic studies of almost 32,000 white individuals of European descent. Results of the comprehensive genetic screening were correlated with participants' serum vitamin D levels. Statistically significant associations were found for four common variants, all in genes coding enzymes involved with the synthesis, breakdown or transport of vitamin D. The risk association was independent of geographic or other environmental factors; and the more variants an individual inherited, the greater the risk of vitamin D deficiency.

Should the recommended daily allowance of vitamin D be based results of genetic tests? Seems like that makes sense.

The big studies done on how diet, lifestyle and other factors influence disease risks should all include collection of genetic samples so that as genetic testing becomes cheaper the DNA of all study participants can be sequenced. An obvious question from this study: Do some of the genetic variants that lower blood vitamin D also increase risk of osteoporosis, cancer, heart disease, or other diseases? Or maybe do any of these genetic variants lower disease risks?

By Randall Parker    2010 June 21 10:36 PM   Entry Permalink | Comments (1)
2008 July 17 Thursday
Gene Determines Benefit Of Eating Broccoli

Why does broccoli reduce the risk of prostate cancer and other disease? Does it deliver that risk reduction for everyone? Sulforaphane found in broccoli and other cruciferous vegetables causes a greater change in gene expression for those with a particular version of the gene GSTM1.

Epidemiological studies suggest that people who consume more than one portion of cruciferous vegetables per week are at lower risk of both the incidence of prostate cancer and of developing aggressive prostate cancer but there is little understanding of the underlying mechanisms. In this study, we quantify and interpret changes in global gene expression patterns in the human prostate gland before, during and after a 12 month broccoli-rich diet.

Methods and Findings

Volunteers were randomly assigned to either a broccoli-rich or a pea-rich diet. After six months there were no differences in gene expression between glutathione S-transferase mu 1 (GSTM1) positive and null individuals on the pea-rich diet but significant differences between GSTM1 genotypes on the broccoli-rich diet, associated with transforming growth factor beta 1 (TGFβ1) and epidermal growth factor (EGF) signalling pathways. Comparison of biopsies obtained pre and post intervention revealed more changes in gene expression occurred in individuals on a broccoli-rich diet than in those on a pea-rich diet. While there were changes in androgen signalling, regardless of diet, men on the broccoli diet had additional changes to mRNA processing, and TGFβ1, EGF and insulin signalling. We also provide evidence that sulforaphane (the isothiocyanate derived from 4-methylsuphinylbutyl glucosinolate that accumulates in broccoli) chemically interacts with TGFβ1, EGF and insulin peptides to form thioureas, and enhances TGFβ1/Smad-mediated transcription.


These findings suggest that consuming broccoli interacts with GSTM1 genotype to result in complex changes to signalling pathways associated with inflammation and carcinogenesis in the prostate. We propose that these changes may be mediated through the chemical interaction of isothiocyanates with signalling peptides in the plasma. This study provides, for the first time, experimental evidence obtained in humans to support observational studies that diets rich in cruciferous vegetables may reduce the risk of prostate cancer and other chronic disease.

If you have the right version of GSTM1 there is good news and there is bad news. The good news is that you can reduce your risk of prostate cancer and other diseases by eating broccoli. The bad news is that you really ought to be eating broccoli.

What would be a useful next step: determine how much consumption of cabbage (or other cruciferous vegetable less undesirable than broccoli) will cause as big a gene expression change as consuming broccoli.

This result illustrates the potential for nutritional genomics to guide personal dietary choices. People swear by different diets as delivering great benefits for them. Well, we are going to discover in the next several years to what extent there is no one ideal diet. Different people will end up having different ideal diets. Cheap DNA testing is going to allow us to find out individually what our best diet would be. There'll be upsides and downsides to knowing this. On one hand, you'll be able to avoid eating some types of food that you do not like that provide benefits for others but not for you. On the other hand, you'll discover that some foods you really do not like are great for you and some foods you do like are bad for you.

By Randall Parker    2008 July 17 10:52 PM   Entry Permalink | Comments (13)
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