Mechanism:

G reduces the ability of PPAR gamma to activate its target genes (decreases transcriptional activity) (R).

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)

Hypertensive and obese G carriers had lower fasting glucose and lower triglycerides than hypertensive and obese CC carriers (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).

One G allele (p=0.0101, OR=1.84) and GG (p=0.0020, OR=2.45) were more commonly found in patients with sarcoidosis (R). Sarcoidosis is caused, in part, by lower PPAR gamma (R).

C (+/FWD) allele='Pro'

rs1801282

Parent Gene: PPARG

Importance: 5
Less common allele: G = 7%
More common allele: C = 93%
My Genotype: Log In
Risk Allele: C, C

Disease/Trait: Type Ii Diabetes Mellitus

The C allele of rs1801282 is reported to be associated with Type Ii Diabetes Mellitus (R) . Your genotype was not identified for this SNP so we are unable to comment on your association with Type 2 diabetes (DGI+FUSION+WTCCC).

Disease/Trait: Body Mass Index

rs1801282 is associated with Body Mass Index (R) . It is reported to association with Fasting insulin-related traits (interaction with BMI). No specific risk allele was identified in the study.

Disease/Trait: Fasting Blood Insulin Measurement

rs1801282 is associated with Fasting Blood Insulin Measurement (R) . It is reported to association with Fasting insulin-related traits (interaction with BMI). No specific risk allele was identified in the study.

Disease/Trait: Type Ii Diabetes Mellitus

The C allele of rs1801282 is reported to be associated with Type Ii Diabetes Mellitus (R) . Your genotype was not identified for this SNP so we are unable to comment on your association with Type 2 diabetes.