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.
Jaziri
Riphed
R
INSERM, U695, Xavier Bichat Medical School, BP 416, 16 rue Henri Huchard, 75870 Paris Cedex 18, France.
Lobbens
Stephane
S
Aubert
Roberte
R
Péan
Franck
F
Lahmidi
Saida
S
Vaxillaire
Martine
M
Porchay
Isabelle
I
Bellili
Naïma
N
Tichet
Jean
J
Balkau
Beverley
B
Froguel
Philippe
P
Marre
Michel
M
Fumeron
Frédéric
F
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