Association of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma2 with decreased basic metabolic rate in women with polycystic ovary syndrome.
OBJECTIVE
The peroxisome proliferator-activated receptor (PPAR)gamma is a transcription factor involved in glucose homeostasis and energy metabolism. A missense mutation at codon 12 in the PPARgamma2 has been associated with increased body mass index (BMI) and attenuated insulin resistance (IR) in polycystic ovary syndrome (PCOS). We have recently shown a decreased basic metabolic rate (BMR) in PCOS. The aim of the present study is to determine the prevalence of the Pro12Ala polymorphism of the PPARgamma2 gene and its associations with indices of IR and BMR in lean and slightly overweight PCOS women.


METHODS
Case-control association study involving 156 PCOS women with biochemical hyperandrogenism, chronic anovulation and polycystic ovarian morphology in ultrasound and 56 unrelated healthy controls.


METHODS
Hormonal determinations were performed by electrochemiluminescence quantitation or RIA. BMR was measured by indirect calorimetry. All subjects were genotyped by a PCR-restriction fragment length polymorphism assay.


RESULTS
Genotype frequencies of the Pro12Ala polymorphism in PPARgamma2 did not differ among PCOS women and control subjects. The presence of Pro12Ala polymorphism of PPARgamma2 was associated with lower BMR (P=0.04). This finding was valid in our subgroup of lean PCOS (BMI<25 kg/m(2)), in which the Ala variant was also associated with higher total testosterone values.


CONCLUSIONS
The Pro12Ala polymorphism in the PPARgamma2 gene is associated with decreased BMR in women with PCOS and biochemical hyperandrogenemia. These young women are therefore at risk to increase their body weight and should restrict their energy intake by diet and enhance their energy expenditure by exercise.
Koika
Vasiliki
V
Division of Reproductive Endocrinology and Department of Obstetrics and Gynecology, University of Patras Medical School, University Hospital, 26500 Patras, Greece.
Marioli
Dimitra J
DJ
Saltamavros
Alexandros D
AD
Vervita
Vasiliki
V
Koufogiannis
Kleanthis D
KD
Adonakis
George
G
Decavalas
George
G
Georgopoulos
Neoklis A
NA
D000328:Adult; D001481:Basal Metabolism / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D020125:Mutation, Missense; D047495:PPAR gamma / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; D047495:PPAR gamma; D013739:Testosterone; D004247:DNA