The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing hyperglycemia over 6 years and combines with the effect of the APM1 G-11391A single nucleotide polymorphism: the Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study.
Although cross-sectional studies have associated the Pro12Ala polymorphism of PPARG with type 2 diabetes, prospective studies offer more opportunities to investigate genetic variants. Associations between PPARG polymorphisms with insulin resistance parameters and with the 6-year incidence of impaired fasting glucose or type 2 diabetes were tested in 3,914 French Caucasians from the DESIR (Data From an Epidemiological Study on the Insulin Resistance Syndrome) cohort. In subjects normoglycemic at baseline (n = 3,498), the 6-year risk of hyperglycemia was lower in PPARG Ala carriers (odds ratio [OR] vs. ProPro = 0.66 [95% CI 0.44-0.99], P = 0.046 adjusted for sex, age, and BMI). Similar results were found with the PPARG C1431T single nucleotide polymorphism (SNP; adjusted OR = 0.65 [0.44-0.96], P = 0.036). Both alleles are in strong linkage disequilibrium (D' = 0.669, P < 0.001). The baseline mean fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in Ala carriers compared with ProPro homozygotes (P = 0.001 for both), with smaller increases in mean insulin and HOMA-IR during follow-up (P = 0.007 and 0.018, respectively). No association with insulin levels or HOMA-IR was found with C1431T. In this cohort, the APM1 G-11391A SNP is associated with the development of hyperglycemia. The combined effects of PPARG Pro12Ala and APM1 G-11391A SNPs showed no interaction on the risk of 6-year hyperglycemia. The PPARG Ala allele showed a relatively high protective effect in developing hyperglycemia and hyperinsulinemia during a 6-year period. Cumulative rather than synergistic effects of PPARG Pro12Ala and APM1 SNPs on diabetes risk are suggested.
INSERM, U695, Xavier Bichat Medical School, BP 416, 16 rue Henri Huchard, 75870 Paris Cedex 18, France.
Riphed
R
Jaziri
Stephane
S
Lobbens
Roberte
R
Aubert
Franck
F
Péan
Saida
S
Lahmidi
Martine
M
Vaxillaire
Isabelle
I
Porchay
Naïma
N
Bellili
Jean
J
Tichet
Beverley
B
Balkau
Philippe
P
Froguel
Michel
M
Marre
Frédéric
F
Fumeron
D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D000409:Alanine; D019943:Amino Acid Substitution; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000235:genetics*; D006946:Hyperinsulinism / Q000453:epidemiology / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics*; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011392:Proline
D052242:Adiponectin; D047495:PPAR gamma; D011392:Proline; D000409:Alanine