Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome.
The Pro12Ala polymorphism of PPAR-gamma 2 has been shown to influence insulin sensitivity and the risk of type 2 diabetes in various ethnic populations. We examined whether the polymorphism was related to the insulin resistance syndrome (IRS) among nondiabetic Danish subjects. The Pro12Ala variant was examined using PCR-restriction fragment length polymorphism in a phenotypically well characterized population-based sample of 2245 nondiabetic subjects. The study participants were characterized by a number of anthropometric and biochemical measurements and the European Group for the Study of Insulin Resistance criteria enabling a classification of the study population in an IRS group and a non-IRS group. The allelic frequency of the Pro12Ala polymorphism in the total study sample was 14% (95% confidence interval, 13-15%). Two hundred ninety-four subjects fulfilled the European Group for the Study of Insulin Resistance criteria defining the IRS. The frequency of the Ala allele was 12.6% in the IRS group and 14.2% among subjects classified as not having the IRS (P = 0.15). However, the frequency of the variant in the homozygous form was significantly lower in the IRS group [0.7% (0-1.6%)] compared with the frequency in the non-IRS group [2.8% (2.1-3.5%); P = 0.02; odds ratio, 0.24 (0.06-0.99)]. Moreover, in the total study population, homozygous carriers of the variant had lower levels of fasting serum triglyceride [1.1 +/- 0.4 mmol/liter (means +/- SD) vs. 1.4 +/- 0.9 mmol/liter; P = 0.04] and a lower diastolic blood pressure (79 +/- 8 mm Hg vs. 82 +/- 11 mm Hg; P = 0.01) compared with wild-type carriers. The same tendency was observed with regard to the homeostasis model assessment estimate of insulin resistance (P = 0.16). There were no differences between genotype groups with respect to measures of body composition (BMI and waist circumference). In conclusion, homozygosity of the codon 12 variant of PPAR-gamma 2 confers a reduced risk of the IRS among Danish Caucasian subjects.
Frederiksen
Laura
L
Department of Endocrinology (L.F., K.B., S.M., S.A.U.) and Clinical Biochemistry (M.F.), Hvidovre University Hospital, Hvidovre DK-2650, Denmark.
Brødbaek
Kasper
K
Fenger
Mogens
M
Jørgensen
Torben
T
Borch-Johnsen
Knut
K
Madsbad
Sten
S
Urhammer
Søren A
SA
D000328:Adult; D000368:Aged; D000409:Alanine / Q000235:genetics; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004198:Disease Susceptibility / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D011392:Proline; D000409:Alanine