title: PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility, related traits, and PON1 activity in Indian women with the syndrome.
abstract: OBJECTIVE
  To investigate the association of paraoxonase 1 (PON1) polymorphisms (L55M and Q192R) with polycystic ovary syndrome (PCOS) susceptibility and its related traits in Indian women.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Academic research institute, infertility, and endocrinology clinics.
  
  
  METHODS
  Controls (n = 326), women with PCOS (n = 482).
  
  
  METHODS
  None.
  
  
  METHODS
  Genotypic and allelic frequency distribution, genotype-phenotype association, different PON1 activities (lactonase, arylesterase, and paraoxonase).
  
  
  RESULTS
  The genotypic and allelic frequency distributions of the L55M polymorphism were significantly different between lean controls and lean women with PCOS, and this polymorphism reduced the risk of PCOS development in lean but not in obese Indian women. Furthermore, this polymorphism was significantly associated with decreased 2-hour glucose, apolipoprotein B, free and bioavailable T, and free androgen index concurrent with increased sex hormone-binding globulin (SHBG) and FSH levels only in lean women with PCOS. However, Q192R polymorphism showed comparable genotypic frequency distribution between controls and women with PCOS. PON1 lactonase and arylesterase activities were significantly decreased in women with PCOS compared with controls. PON1 polymorphisms were shown to influence its activities.
  
  
  CONCLUSIONS
  Our study showed that L55M, but not Q192R, polymorphism is significantly associated with reduced PCOS susceptibility only in lean women and also impacts glucose metabolism, lipid parameters, and hyperandrogenemia in them. Our study therefore suggests the possibility of differential genetic pathophysiology of PCOS between lean and obese women.
authors.affiliation: Department of Molecular Endocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Roshan
authors.initials: R
authors.lastname: Dadachanji
authors.affiliation: Department of Molecular Endocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Shaikh
authors.affiliation: Department of Molecular Endocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Sushma
authors.initials: S
authors.lastname: Khavale
authors.affiliation: Department of Clinical Research, National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Anushree
authors.initials: A
authors.lastname: Patil
authors.affiliation: Department of Endocrinology, Seth GS Medical College, Mumbai, India.
authors.forename: Nalini
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Molecular Endocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai, India. Electronic address: mukherjees@nirrh.res.in.
authors.forename: Srabani
authors.initials: S
authors.lastname: Mukherjee
mesh_terms: D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001835:Body Weight / Q000502:physiology; D016022:Case-Control Studies; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: L55M; PCOS; PON1 activity; PON1 gene; Q192R; hyperandrogenemia