Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome

Heath J. Antoine, Marita Pall, Belynda C. Trader, Yii Der I. Chen, Ricardo Azziz, Mark O. Goodarzi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)862-869
Number of pages8
JournalFertility and sterility
Volume87
Issue number4
DOIs
StatePublished - Apr 1 2007

Fingerprint

Polycystic Ovary Syndrome
PPAR gamma
Insulin Resistance
Testosterone
Alleles
Genotype
Modifier Genes
Phenotype
Los Angeles
Endocrinology
Linkage Disequilibrium
Haplotypes
Androgens
Exons
Homeostasis
Outcome Assessment (Health Care)

Keywords

  • Peroxisome proliferator-activated receptor gamma
  • insulin resistance
  • polycystic ovary syndrome
  • single-nucleotide polymorphism
  • testosterone

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome. / Antoine, Heath J.; Pall, Marita; Trader, Belynda C.; Chen, Yii Der I.; Azziz, Ricardo; Goodarzi, Mark O.

In: Fertility and sterility, Vol. 87, No. 4, 01.04.2007, p. 862-869.

Research output: Contribution to journalArticle

Antoine, Heath J. ; Pall, Marita ; Trader, Belynda C. ; Chen, Yii Der I. ; Azziz, Ricardo ; Goodarzi, Mark O. / Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome. In: Fertility and sterility. 2007 ; Vol. 87, No. 4. pp. 862-869.
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abstract = "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.",
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AU - Pall, Marita

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AU - Chen, Yii Der I.

AU - Azziz, Ricardo

AU - Goodarzi, Mark O.

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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.

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