Beta Carotene May Protect People with Common Genetic Risk Factor for Type 2 DiabetesWednesday, February 20, 2013
Stanford University School of Medicine investigators have found that for people harboring a genetic predisposition that is prevalent among Americans, beta-carotene, which the body converts to a close cousin of vitamin A, may lower the risk for the most common form of diabetes, while gamma tocopherol, the major form of vitamin E in the American diet, may increase risk for the disease.
The scientists used a "big data" approach to hunt down interactions between gene variants previously associated with increased risk for type 2 diabetes and blood levels of substances previously implicated in type 2 diabetes risk. In people carrying a double dose of one such predisposing gene variant, the researchers pinpointed a highly statistically significant inverse association of beta carotene blood levels with type 2 diabetes risk, along with a suspiciously high positive association of gamma tocopherol with risk for the disease.
"Type 2 diabetes affects about 15 percent of the world`s population, and the numbers are increasing," said Atul Butte, MD, PhD, associate professor of systems medicine in pediatrics. "Government health authorities estimate that one-third of all children born in the United States since the year 2000 will get this disease at some point in their lives, possibly knocking decades off their life expectancies."
Butte is the senior author of the new study, which was recently published in Human Genetics. The first author, Chirag Patel, PhD, is a former graduate student in Butte`s lab and now a postdoctoral scholar at the Stanford Prevention Research Center.
The findings point the way to further experiments that could establish whether beta-carotene and gamma tocopherol are, respectively, protective and harmful themselves, or merely "markers" whose blood levels dovetail with the presence or absence of some other substance, process or defect that is a true causal factor.
Moreover, the fact that both beta-carotene and gamma tocopherol interact with the same gene variant to influence diabetes risk, albeit in opposite directions, suggests that the protein the gene called, SLC30A4, codes for may play a crucial role in the disease. Indeed, that protein is relatively abundant in insulin-producing islet cells of the pancreas, where it aids the transport of zinc into those cells. This, in turn, triggers the release of insulin, whose adequate secretion by the pancreas and efficient uptake in muscle, liver and fat tissue counters the dangerous buildup of glucose in the blood and, in the long run, the onset of type 2 diabetes.
The genomes of some 50 to 60 percent of the U.S. population carry two copies of that very gene variant, which previous studies have shown to confer a slightly increased risk of contracting type 2 diabetes. This variant was one of 18, each found by other researchers to have a mild association with type 2 diabetes risk, that the Butte team incorporated into its analysis.
These gene/disease connections had been identified via so-called "genome-wide association studies," or GWAS. In such analyses, the genomes of large numbers of people with a disease are compared with those of people without it to see if certain versions of any gene variants occur with substantially greater frequency in one group than in the other.
The most well-studied gene variations are substitutions of one type of chemical unit of DNA for another one at a single position along the genome. "It`s like a single-letter spelling change," said Butte. "`Grey` versus `gray` may not matter much, if at all. But when `grey` turns into `grew,` you might have some serious semantic issues." The genome contains millions of spots at which such differences occur, so advanced statistical techniques must be employed to screen out "frequency differences" between the "diseased" and "healthy" groups that are, at bottom, the mere results of blind chance.
"While plenty of genetic risk factors for type 2 diabetes have been found," said Butte, "none of them taken alone, and not even all of them taken together, comes close to accounting for the prevalence of type 2 diabetes." But genes don`t act in a vacuum, he added. (If food is hard to find, nobody gets fat, obesity predisposition or not.)