The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been associated with decreased risk of diabetes and obesity, both disorders linked to cognitive impairment.
These results suggest that the Pro12Ala mutation in PPARgamma is not associated with either diabetes or obesity and may not be an important determinant of obesity or diabetes in Korean subjects.
There appears to be certain genes which predispose Indians to diabetes while other genes (for example Pro 12 Ala polymorphism of PPAR gamma gene) which afford protection against diabetes and insulin resistance to Caucasians, do not appear to protect Indians.
In a randomized, placebo-controlled, double-blind, crossover study, 24 subjects with type 2 diabetes and one subject with partial lipodystrophy and diabetes due to dominant-negative mutation in the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene (P467L) received placebo and rosiglitazone for 3 months.
In subgroup analyses, the +276 genotype was significantly associated with diabetes risk only among subjects with peroxisome proliferator-activated receptor-gamma (PPAR gamma) variant 12Ala allele (OR comparing +276 T alleles with the G/G genotype = 1.69, 1.04-2.75, P = 0.035) or among obese subjects (1.46, 1.03-2.08, P = 0.03).
Another PPARγ polymorphism, the C1431T, is in strong linkage disequilibrium with Pro12Ala and has been shown to be associated with body weight, but its association with diabetes is controversial.
Furthermore, women carrying the C allele of rs6902123 of PPARD and the Pro12Pro genotype of the PPAR-gamma2 gene (PPARG2) had a 3.9-fold (95% CI 1.79-8.63; P = 0.001)-higher risk for diabetes than women with protective genotypes.
Genetic polymorphism of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala on ethnic susceptibility to diabetes in Uygur, Kazak and Han subjects.
The allele frequencies for a Pro12-->Ala substitution in peroxisome proliferator-activated receptor-gamma differ among ethnic groups, and its relationship with diabetes and associated diseases is controversial.
The C1431T polymorphism in peroxisome proliferator-activated receptor-γ (PPARγ) has been shown to be associated with diabetes, obesity, and metabolic syndrome.
The genetic influence of PPARGP12A genotype is modest and is overshadowed by duration of diabetes and systolic blood pressure as the major risk factors for diabetic nephropathy in the Oji-Cree population.
The Gly482Ser variant in the peroxisome proliferator-activated receptor gamma coactivator-1 is not associated with diabetes-related traits in non-diabetic German and Dutch populations.
Single nucleotide polymorphisms (SNPs) in diabetes related peroxisome proliferator-activated receptor gamma (PPARG) gene were investigated with a case-control approach.
Loss-of-function mutations in PPARG result in familial partial lipodystrophy subtype 3 (FPDL3), a rare condition characterized by aberrant adipose tissue distribution and severe metabolic complications, including diabetes.
Interestingly, five positional candidate genes for diabetes and related complications are located in our linkage region (the pituitary adenylate cyclase activating polypeptide (PACAP in 18p11); the peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1 in 4p15); PTEN, PPP1R5, and IDE located in 10q23.
Yet unidentified variants within the peroxisome proliferator-activated receptor gamma (PPARgamma) 2 promoter may explain the inconsistent reports on associations between variants in the coding region and obesity or diabetes.
The authors highlight these challenges and biases using an illustrative example: meta-analysis of interactions between the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma (PPARgamma) gene and various diet and lifestyle factors in the risk of diabetes.