The root causes of complex diseases such as Type 2 diabetes and obesity have been difficult to identify because the diseases are very complex. They occur at the dicey biological intersection of genes and environment and, because they arose in our relatively recent past, it's not easy to simply compare DNA sequences from "then" and "now" to pinpoint likely genetic culprits.
People with the "new" variants, which are thought to have first occurred 2,000 to 12,000 years ago, have higher fasting levels of blood glucose than those with the more traditional, or ancestral, form of the gene. High blood glucose levels are associated with the development of diabetes, which occurs when the body is unable to produce or respond properly to insulin.
The finding may help scientists better understand the subtle changes in human metabolism, or "energy balance regulation," that occurred as our species shifted from being primarily hunter-gatherers to a more agriculturally based society. It may also help clinicians identify individuals likely to develop diabetes, and direct the development of new therapies for diabetes and obesity.
Sheau Yu "Teddy" Hsu, PhD, assistant professor of obstetrics and gynecology and senior author of the study, was quoted as saying, "These studies are fascinating because it shows how much the selection process has affected human energy-balance regulation in just a few thousand years and how complex it could be for the future practice of personalized medicine."
He and his colleagues identified three individual changes in the regulatory region of GIP -- that is, the DNA adjacent to the GIP gene that affects when and how it is translated into protein -- that reduced the levels of the hormone. What's more, these three also tended to occur with another mutation in the coding region that results in a slightly different form of the protein. This alternate form is degraded more slowly in human blood.
"Like other humans at the time, the Eurasian population really had to fight for survival," said Hsu.
"Now we're starting to pinpoint how they did that on a molecular level. These gene variants, and the resulting higher blood sugar levels it fostered, may have helped women maintain successful pregnancies in the face of the inevitable famines that occur in an agriculturally based society. Now, in a more food-secure environment, variations in GIP could contribute to the development of diabetes or obesity."
Diabetes, February 7, 2011