title: Gly972Arg of IRS-1 and Lys121Gln of PC-1 polymorphisms act in opposite way in polycystic ovary syndrome.
abstract: OBJECTIVE
  Polycystic ovary syndrome (PCOS) was associated with a number of polymorphisms of genes involved in insulin signaling. So far, they have been studied separately. The aim of this study was to verify the impact of the coexistence of two polymorphisms of insulin signaling.
  
  
  METHODS
  One hundred consecutive PCOS women (diagnosed by Rotterdam criteria) and 45 age-matched healthy women were genotyped for two polymorphisms: Gly972Arg of IRS-1 and Lys121Gln of PC-1. Also, they underwent clinical evaluation, blood sampling for measurement of metabolic and hormonal indices, and a 75-g oral glucose tolerance test (OGTT).
  
  
  RESULTS
  Comparing PCOS women with controls, the rate of homo-/heterozygosity was significantly greater (50 vs. 24.5%, P = 0.004) for IRS-1 polymorphism, but insignificantly greater (20 vs. 13.3%, P = 0.33) for PC-1 polymorphism. In PCOS women, compared with controls, the genotypes IRS-1 hetero/PC-1 wild type (WT) (36 vs. 17.8%, P = 0.03) and IRS-1 hetero/PC-1 hetero (14 vs. 6.7%, P = 0.20) were overrepresented at the expense of IRS-1 WT/PC-1 WT (44 vs. 68.8%, P = 0.005), while IRS-1 WT/PC-1 hetero was similarly represented (6 vs. 6.7%). Based on genotype, metabolic and hormonal indices changed significantly. For instance, six indices (HOMA-IR, fasting insulin, insulin area under the curve at OGTT, triglycerides, total and calculated free testosterone) were the highest in IRS-1 hetero/PC-1 WT women.
  
  
  CONCLUSIONS
  Genetic variations in insulin signaling contribute to the extent and the variability of metabolic and hormonal derangement.
authors: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy.
authors: M A
authors: MA
authors: Pappalardo
authors: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy. roberto.vita@yahoo.it.
authors: R
authors: R
authors: Vita
authors: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy.
authors: F
authors: F
authors: Di Bari
authors: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Viale Gazzi, 98125, Messina, Italy.
authors: M
authors: M
authors: Le Donne
authors: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy.
authors: F
authors: F
authors: Trimarchi
authors: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy.|Master Program on Childhood, Adolescence and Women's Endocrine Health, University of Messina, Viale Gazzi, 98125, Messina, Italy.|Interdepartmental Program of Molecular and Clinical Endocrinology and Women's Endocrine Health, A.O.U. Policlinico G. Martino, Viale Gazzi, 98125, Messina, Italy.
authors: S
authors: S
authors: Benvenga
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D050396:TRPP Cation Channels; C526292:IRS1 protein, human
keywords: IRS-1; Insulin resistance; PC-1; Polycystic ovary syndrome; Polymorphisms