The minor G allele is associated with:
- lower PPAR gamma activity,
- more benefits to exercise . Having one G allele makes you more responsive to the beneficial health effects of exercise (R).
- increased obesity rates
- lower heart disease,
- lower risk for diabetes,
- poor response to a high-fat diet,
- protective against colorectal cancer,
- protective against psoriatic arthritis.
- higher risk for rheumatoid arthritis
- higher risk for sarcoidosis.
For this SNP, The effect on the individual is weak, but because over 75% of people have the high-risk C allele, the population-attributable risk is enormous (R).
A moderate reduction in PPAR-gamma as a result of the polymorphism decreases the release of insulin-desensitizing free fatty acids, tumor necrosis factor-alpha, and resistin and increases the release of the insulin-sensitizing hormone adiponectin, which results in improvement of insulin sensitivity of glucose uptake and suppression of glucose production (R).
Once diabetes has developed, the protective effect of the G allele may be lost, since increased vascular complications and more pronounced beta-cell dysfunction have been reported from the G allele (R).
The G allele has been associated with improved insulin sensitivity and a lower risk for type 2 diabetes in several studies. But these associations are not as strong in obese subjects. Some researchers have found that, among obese subjects, the G allele is associated with increased weight gain (R).
In mice, the G allele did worse with a diet high in fat (58% of calories). The researchers suggest that diet affects the PPARG protein interactions with hormones and other molecules involved in metabolism. When an animal (mouse or human) eats a normal diet, the C version of the PPARG protein is more efficient at storing fat than the G version. But in animals that take in more energy than they expend, the G version of the protein ends up being more pro-fat/weight gain (note, the study was done using transfat) (R).
G is protective against colorectal cancer but associated with gastric cancer. (R)
G was also associated with lower heart disease, with a 90% risk reduction for ischemic heart disease and a 76% reduction of vascular death. Having two G's was the most protective (R).
G is protective against psoriatic arthritis (R).
GG was more common in people with rheumatoid arthritis (R).
C (+/FWD) allele='Pro'