title: Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome.
abstract: OBJECTIVE
  Peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in glucose and lipid metabolism is one of the candidate genes associated with polycystic ovary syndrome (PCOS). We investigated individual and combined associations of Pro12Ala and His447His polymorphisms of PPARγ with PCOS susceptibility and its related traits (hyperinsulinemia, hyperandrogenemia and lipid parameters) in Indian women.
  
  
  METHODS
  Genotyping of PPARγ polymorphisms in this case-control study was performed in PCOS (n = 450) and age-matched controls (n = 300) by direct sequencing. Clinical, anthropometric, hormonal and metabolic parameters were estimated in 275 women with PCOS and 169 controls. Chi-square test was used to compare the categorical data while regression analysis was used to evaluate association of genotypes with PCOS as well as its related phenotypes.
  
  
  RESULTS
  The frequencies of CC and CG + GG genotypes of Pro12Ala (χ² = 15.3, p < 0.0001) and CC and CT + TT genotypes of His447His (χ² = 12.7, p = 0.0004) polymorphisms were significantly different between PCOS and controls. Logistic regression analysis revealed a significant association of PCOS with Pro12Ala but not the His447His polymorphism. Carriers of variant genotypes at both PPARγ loci showed significantly reduced 2 h glucose levels while carriers of variant His447His genotype showed lower fasting insulin and HOMA-IR levels in PCOS women.
  
  
  CONCLUSIONS
  Pro12Ala polymorphism of PPARγ showed significant association with decreased PCOS susceptibility. Both polymorphisms influenced insulin related traits (2 h glucose, fasting insulin and HOMA-IR) and improved glucose metabolism in these women. This is the first report to establish that variations in PPARγ gene influence the insulin resistance pathophysiology in Indian women with PCOS.
authors.affiliation: Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, J. M. Street, Parel Mumbai 400012, India. s.nuzhat@yahoo.co.in
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Shaikh
authors.forename: Ankur
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Nalini
authors.initials: N
authors.lastname: Shah
authors.forename: Pervin
authors.initials: P
authors.lastname: Meherji
authors.forename: Srabani
authors.initials: S
authors.lastname: Mukherjee
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics*; D007194:India; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D007328:Insulin; D047495:PPAR gamma; D005947:Glucose