The peroxisome proliferator-activated receptor-gamma2 Pro12A1a variant: association with type 2 diabetes and trait differences.
Recent studies have identified a common proline-to-alanine substitution (Pro12Ala) in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), a nuclear receptor that regulates adipocyte differentiation and possibly insulin sensitivity. The Pro12Ala variant has been associated in some studies with diabetes-related traits and/or protection against type 2 diabetes. We examined this variant in 935 Finnish subjects, including 522 subjects with type 2 diabetes, 193 nondiabetic spouses, and 220 elderly nondiabetic control subjects. The frequency of the Pro12Ala variant was significantly lower in diabetic subjects than in nondiabetic subjects (0.15 vs. 0.21; P = 0.001). We also compared diabetes-related traits between subjects with and without the Pro12Ala variant within subgroups. Among diabetic subjects, the variant was associated with greater weight gain after age 20 years (P = 0.023) and lower triglyceride levels (P = 0.033). Diastolic blood pressure was higher in grossly obese (BMI >40 kg/m2) diabetic subjects with the variant. In nondiabetic spouses, the variant was associated with higher fasting insulin (P = 0.033), systolic blood pressure (P = 0.021), and diastolic blood pressure (P = 0.045). These findings support a role for the PPAR-gamma2 Pro12Ala variant in the etiology of type 2 diabetes and the insulin resistance syndrome.
Douglas
J A
JA
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor 48109-2029, USA.
Erdos
M R
MR
Watanabe
R M
RM
Braun
A
A
Johnston
C L
CL
Oeth
P
P
Mohlke
K L
KL
Valle
T T
TT
Ehnholm
C
C
Buchanan
T A
TA
Bergman
R N
RN
Collins
F S
FS
Boehnke
M
M
Tuomilehto
J
J
D000368:Aged; D001794:Blood Pressure; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005215:Fasting / Q000097:blood; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain
D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides