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. DESIGN: 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. CONCLUSION: 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.

Renal dysgenesis and KAL1 gene defects in patients with sporadic Kallmann syndrome.

OBJECTIVE: To correlate the presence of renal agenesis/dysgenesis to the prevalence of KAL1 gene defects in patients with sporadic Kallmann syndrome (KS). DESIGN: Prospective assessment of renal structure and DNA sequence analysis of the KAL1 gene. SETTING: Outpatient clinics of the divisions of endocrinology of university hospitals. PATIENT(S): Sixteen male patients with sporadic KS. INTERVENTION(S): Assessment of renal structure by abdominal ultrasounds scans and DNA extraction, polymerase chain reaction amplification, and DNA sequence analysis of all 14 exons of the KAL1 gene. MAIN OUTCOME MEASURE(S): KAL 1 gene structure and presence of renal dysgenesis. RESULT(S): Renal dysgenesis was identified in only two of 16 KS patients. Genetic defects were found in only two patients with KS, that is, in those with the identified renal dysgenesis. The first gene defect was identified in a patient with associated right renal agenesis who had two point mutations in the KAL1 gene: the first was a G to A transition in exon 11, turning codon 514 encoding glutamic acid into lysine; and the second was a G to A transition in exon 13, turning codon 660 encoding alanine into threonine. The second gene defect was identified in a patient with ichthyosis, right renal agenesis, and mirror movements of the upper limbs (synkinesia) and comprised a deletion of exons 5-10 of the KAL1 gene and a complete deletion of the steroid sulphatase gene. CONCLUSION(S): The phenotype of renal agenesis/dysgenesis strongly indicates the existence of KAL1 gene defects in the genotype of patients with sporadic KS, providing evidence for the X-linked mode of inheritance and offering the opportunity for genetic counseling.

alpha 2 beta adrenoreceptor 301-303 deletion polymorphism in polycystic ovary syndrome.

alpha(2beta) adrenoreceptor 301-303 deletion polymorphism does not influence basal metabolic rate, insulin resistance or weight gain in Greek women with polycystic ovary syndrome.