Diabetes, obesity and genetics

An article in Nature finds that variations in 4 specific genes (TCF7L2, SLC30A8, IDE–KIF11–HHEX and EXT2–ALX4) can explain 70% of who gets diabetes.  It makes you wonder why people have those gene variants to begin with.  What purpose do they serve?

Also, newly published research in Science shows that having a variant (or two copies) of the so-called FATSO gene can often lead to obesity.

I'm wondering if the susceptibility to diabetes is similar to that of hypertension (due to a salt imbalance).  An article a couple of years ago described how variants in the CYP3A gene are linked to salt retention in the body.  Africans who live near the equator have one form of the gene, and others (living farther from the equator) have another form of the gene!  According to a press release at that time:

In the sub-Saharan African regions where humans first appeared, available salt must have been limited and quickly lost through sweat. People who were better at retaining salt may have had a significant survival advantage.

The problem is (and anyone who's stopped by McDonalds for super-size fries well knows), salt is no longer scarce in the modern world.  So people with the stronger "salt retention" version of the gene are at greater risk for hypertension these days.

Evolution is about trade-offs.  Having the genes for better salt retention in warm climates can give you hypertension in the era of fast food.  Does diabetes work the same way?

“This could change the way we look for disease genes,” [said study author Anna Di Rienzo, Associate Professor in Human Genetics]. “Historically, we have searched for mutations, altered or damaged versions of genes that cause rare disorders, like cystic fibrosis or phenylketonuria. Now, we are starting to look for common genes that may have been beneficial in an environment of scarcity, but have become harmful in a world of plenty. In the modern setting, it may often be the genes that aren’t damaged that predispose to disease, such as the ‘thrifty genes’ associated with type 2 diabetes.”