TY - JOUR
T1 - Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome
AU - Antoine, Heath J.
AU - Pall, Marita
AU - Trader, Belynda C.
AU - Chen, Yii Der I.
AU - Azziz, Ricardo
AU - Goodarzi, Mark O.
N1 - Funding Information:
Supported in part by the Helping Hand of Los Angeles, Los Angeles, California, and by grants R01-HD29364 and K24-HD01346 from the National Institutes of Health, Bethesda, Maryland (R.A.).
PY - 2007/4
Y1 - 2007/4
N2 - Objective: To investigate the relationship of the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala and silent exon 6 (His447His) polymorphisms with the clinical features of polycystic ovary syndrome (PCOS). Design: Patients with PCOS and control subjects were genotyped for Pro12Ala and His447His. Associations between genotype, diagnosis, and hormonal/metabolic parameters were assessed. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham, Birmingham, Alabama. Control subjects were recruited from the surrounding community. Genotyping was performed at the Cedars-Sinai Medical Center in Los Angeles, California. Patient(s): Participants included 285 white women with PCOS and 187 controls. Intervention(s): None. Main Outcome Measure(s): The Pro12Ala and His447His genotypes, and hormonal and metabolic phenotypes. Result(s): The Pro12Ala and His447His genotypes did not influence risk of PCOS or its component phenotypes in patients with PCOS. In controls, Pro12Ala did not influence measures of insulin resistance or androgen production. However, carriers of the His447His T-allele had significantly decreased free and total T levels, and a significantly decreased homeostasis model assessment index of insulin resistance. Furthermore, haplotypes in controls bearing the His447His T-allele were also associated with decreased T. Conclusion(s): Peroxisome proliferator-activated receptor gamma does not appear to be an important modifier gene in PCOS. In controls, however, the His447His T-allele may be in linkage disequilibrium with a functional variant that influences insulin resistance and T production.
AB - Objective: To investigate the relationship of the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala and silent exon 6 (His447His) polymorphisms with the clinical features of polycystic ovary syndrome (PCOS). Design: Patients with PCOS and control subjects were genotyped for Pro12Ala and His447His. Associations between genotype, diagnosis, and hormonal/metabolic parameters were assessed. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham, Birmingham, Alabama. Control subjects were recruited from the surrounding community. Genotyping was performed at the Cedars-Sinai Medical Center in Los Angeles, California. Patient(s): Participants included 285 white women with PCOS and 187 controls. Intervention(s): None. Main Outcome Measure(s): The Pro12Ala and His447His genotypes, and hormonal and metabolic phenotypes. Result(s): The Pro12Ala and His447His genotypes did not influence risk of PCOS or its component phenotypes in patients with PCOS. In controls, Pro12Ala did not influence measures of insulin resistance or androgen production. However, carriers of the His447His T-allele had significantly decreased free and total T levels, and a significantly decreased homeostasis model assessment index of insulin resistance. Furthermore, haplotypes in controls bearing the His447His T-allele were also associated with decreased T. Conclusion(s): Peroxisome proliferator-activated receptor gamma does not appear to be an important modifier gene in PCOS. In controls, however, the His447His T-allele may be in linkage disequilibrium with a functional variant that influences insulin resistance and T production.
KW - Peroxisome proliferator-activated receptor gamma
KW - insulin resistance
KW - polycystic ovary syndrome
KW - single-nucleotide polymorphism
KW - testosterone
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U2 - 10.1016/j.fertnstert.2006.10.006
DO - 10.1016/j.fertnstert.2006.10.006
M3 - Article
C2 - 17141766
AN - SCOPUS:34047245082
SN - 0015-0282
VL - 87
SP - 862
EP - 869
JO - Fertility and sterility
JF - Fertility and sterility
IS - 4
ER -