title: Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS).
abstract: BACKGROUND
  The polycystic ovary syndrome (PCOS), a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR) and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM) on metabolic and PCOS-specific traits in patients with PCOS.
  
  
  METHODS
  We conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria) using single nucleotide polymorphisms (SNPs) in or in proximity to the fat mass and obesity associated gene (FTO), insulin-induced gene-2 (INSIG2), transcription factor 7-like 2 gene (TCF7L2) and melanocortin 4 receptor gene (MC4R). To compare the effect of FTO obesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4).
  
  
  RESULTS
  The FTO risk allele was associated with IR traits and measures of increased body weight. In addition, the TCF7L2 SNP was associated with body weight traits. For the SNPs in the vicinity of INSIG2 and MC4R and for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect of FTO intron 1 SNP rs9939609 on BMI was +1.56 kg/m2, whereas it was +0.46 kg/m2 in females of the same age range from the general population as shown previously.
  
  
  CONCLUSIONS
  The stronger effect on body weight of the FTO SNP in PCOS might well have implications for the etiology of the disease.
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Tan
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.forename: Onno Eilard
authors.initials: OE
authors.lastname: Janssen
authors.forename: Susanne
authors.initials: S
authors.lastname: Hahn
authors.forename: Harald
authors.initials: H
authors.lastname: Lahner
authors.forename: Tiina
authors.initials: T
authors.lastname: Dietz
authors.forename: Susann
authors.initials: S
authors.lastname: Scherag
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Carla Ivane Ganz
authors.initials: CI
authors.lastname: Vogel
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Klaus
authors.initials: K
authors.lastname: Mann
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
mesh_terms: D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001483:Base Sequence; D015992:Body Mass Index; D017931:DNA Primers / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D051820:TCF Transcription Factors / Q000235:genetics; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D017931:DNA Primers; C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C470072:MC4R protein, human; D008565:Membrane Proteins; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human