Working in the laboratory, the scientists isolated fragments of DNA in cells to study the effects of exposure to calcitriol, the “active” form of vitamin D. Their findings are published in the journal Genome Research.
Vitamin D influences DNA through a “go-between” protein called the vitamin D receptor (VDR). The protein is activated by the vitamin and attaches itself to DNA at the binding sites the researchers identified. VDR binding was enriched in disease-associated regions of the genetic code and also areas linked to traits such as tanning, height and hair colour.
Study leader Dr Sreeram Ramagopalan, from the Wellcome Trust Centre for Human Genetics, at Oxford University, said: “There is now evidence supporting a role for vitamin D in susceptibility to a host of diseases. Vitamin D supplements during pregnancy and the early years could have a beneficial effect on a child's health in later life. “Some countries, such as France, have instituted this as a routine public health measure.”
Vitamin D is chiefly made in the body as a result of the skin's exposure to sunlight. A small number of foods also contain the vitamin, including oily fish and eggs, but 90% comes from being in the sun. In many northern countries, a lack of sun can lead to vitamin D deficiency. Over-zealous use of sunscreen can also prevent vitamin D production. It is estimated that more than half the UK population do not get enough vitamin D, and worldwide a billion people may be deficient in the vitamin. Lack of vitamin D affects bone growth and development, leading to rickets in children and bone fractures in adults.
The study supports the theory that lighter, more sun-sensitive skins evolved as people migrated north out of Africa to maximise vitamin D production in the body. A significant number of the VDR binding sites were in DNA regions where genetic changes are commonly found in people of European and Asian descent.
“Vitamin D status is potentially one of the most powerful selective pressures on the genome in relatively recent times,” said co-author Professor George Ebers, also from the Wellcome Trust Centre for Human Genetics. “Our study appears to support this interpretation and it may be we have not had enough time to make all the adaptations we have needed to cope with our northern circumstances.”
Researchers employed imaging techniques to examine and analyze brain anatomical differences between 55 female IBS patients and 48 female control subjects. Patients had moderate IBS severity, with disease duration from one to 34 years (average 11 years). The average age of the participants was 31.
Investigators found both increases and decreases of brain grey matter in specific cortical brain regions.
Even after accounting for additional factors such as anxiety and depression, researchers still discovered differences between IBS patients and control subjects in areas of the brain involved in cognitive and evaluative functions, including the prefrontal and posterior parietal cortices, and in the posterior insula, which represents the primary viscerosensory cortex receiving sensory information from the gastrointestinal tract.
“The grey-matter changes in the posterior insula are particularly interesting since they may play a role in central pain amplification for IBS patients,” said study author David A. Seminowicz, Ph.D., of the Alan Edwards Centre for Research on Pain at McGill University. “This particular finding may point to a specific brain difference or abnormality that plays a role in heightening pain signals that reach the brain from the gut.”
Decreases in grey matter in IBS patients occurred in several regions involved in attentional brain processes, which decide what the body should pay attention to. The thalamus and midbrain also showed reductions, including a region – the periaqueductal grey – that plays a major role in suppressing pain.
“Reductions of grey matter in these key areas may demonstrate an inability of the brain to effectively inhibit pain responses,” Seminowicz said.
The observed decreases in brain grey matter were consistent across IBS patient sub-groups, such as those experiencing more diarrhea-like symptoms than constipation.
“We noticed that the structural brain changes varied between patients who characterized their symptoms primarily as pain, rather than non-painful discomfort,” said Mayer, director of the UCLA Center for Neurobiology of Stress. “In contrast, the length of time a patient has had IBS was not related to these structural brain changes.”
Mayer added that the next steps in the research will include exploring whether genes can be identified that are related to these structural brain changes. In addition, there is a need to increase the study sample size to address male-female differences and to determine if these brain changes are a cause or consequence of having IBS.
The study was funded by the National Institutes of Health.
Additional authors include M. Catherine Bushnell, Ph.D., of McGill University, and Jennifer B. Labus, Joshua A. Bueller, Kirsten Tillisch and Bruce D. Naliboff, Ph.D., all of UCLA.