title: Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study.
abstract: OBJECTIVE
  The weight lowering potential of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP-1R on body weight response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has not yet been evaluated.
  
  
  METHODS
  Fifty-seven obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m(2)) were assigned to liraglutide 1.2 mg QD s.c. for 12 weeks and classified as strong responders regarding weight loss if they lost 5% or more of their initial body weight. They were genotyped for common GLP-1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of measures of obesity were measured before and at the end of the treatment.
  
  
  RESULTS
  Twenty out of 57 subjects were strong responders and lost 7.38 ± 1.74 compared to 2.11 ± 2.17 kg lost in poor responders. Carriers of at least one polymorphic rs10305420 allele had poor treatment response compared to carriers of two wild type alleles (OR = 0.27, 95% CI = 0.09-0.85, P = 0.025). Carriers of at least one polymorphic rs6923761 allele tended to have stronger treatment response compared to carriers of two wild type alleles (OR = 3.06, 95% CI = 0.96-9.74, P = 0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT) comparably decreased in both groups when compared to baseline, whereas no within treatment differences were found in androgen profile. Gastrointestinal adverse events were transit and balanced between strong and poor responders.
  
  
  CONCLUSIONS
  GLP-1R rs10305420 polymorphism explained some of the inter-individual differences in response to liraglutide regarding weight loss in obese PCOS women.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloska 7, 1525, Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Jensterle
authors.forename: Boštjan
authors.initials: B
authors.lastname: Pirš
authors.forename: Katja
authors.initials: K
authors.lastname: Goričar
authors.forename: Vita
authors.initials: V
authors.lastname: Dolžan
authors.forename: Andrej
authors.initials: A
authors.lastname: Janež
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics*; D006801:Humans; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D000069450:Liraglutide / Q000009:adverse effects / Q000627:therapeutic use*; D016015:Logistic Models; D009765:Obesity / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D010865:Pilot Projects; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017524:Slovenia; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects*; D055815:Young Adult; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D000069450:Liraglutide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists