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Horm Metab Res 2011; 43(11): 743-747
DOI: 10.1055/s-0031-1286279
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Susceptibility Loci for Polycystic Ovary Syndrome on Chromosome 2p16.3, 2p21, and 9q33.3 in a Cohort of Caucasian Women

E. Lerchbaum
1   Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
,
O. Trummer
1   Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
,
A. Giuliani
2   Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria
,
H.-J. Gruber
3   Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
,
T. R. Pieber
1   Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
,
B. Obermayer-Pietsch
1   Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
› Author Affiliations
Further Information

Publication History

received 09 May 2011

accepted 03 August 2011

Publication Date:
18 October 2011 (online)

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Abstract

In a recent genome-wide association study investigating Han Chinese PCOS women 3 loci that are strongly associated with PCOS were identified on chromosome 2p16.3 (rs13405728), 2p21 (rs13429458), and 9q33.3 (rs2479106). The aim of the study was to investigate the impact of rs13405728, rs13429458, and rs2479106 variants on PCOS susceptibility in a Caucasian cohort of PCOS and control women. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed in 545 PCOS and 317 control women. The rs13405728, rs13429458, and rs2479106 polymorphisms were genotyped. There was no significant difference in genotype frequencies of rs13405728 and rs13429458 variants between PCOS and controls. There was a trend towards an association of the rs2479106 variant with PCOS susceptibility (p=0.053). PCOS women with the rs2479106 GG genotype had significantly higher WHR than PCOS women carrying the AG and AA genotype (p=0.034 and p=0.020, respectively). Moreover, QChol/HDL and LDL levels were significantly higher in PCOS women carrying the rs2479106 GG genotype when compared to those carrying the AA genotype (p=0.024 and p=0.035, respectively). PCOS women carrying the G allele of rs13405728 had significantly higher AUCgluc, glucose-30 min, and AUCins levels than those carrying the AA genotype (p=0.039, p=0.047, and p=0.044, respectively). In PCOS women, rs13405728 genotypes are associated with glucose and insulin metabolism. Moreover, rs2479106 genotypes were associated with increased WHR levels and an adverse serum lipid profile. Further, we observed a trend towards decreased PCOS susceptibility within carriers of the rs2479106 G-allele. Further studies in large Caucasian PCOS cohorts are warranted to confirm our findings.

Key words

PCOS - genetics - glucose metabolism
 

  • References

  • 1 Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011; 7: 219-231
    CrossrefPubMedGoogle Scholar
  • 2 Broekmans FJ, Knauff EA, Valkenburg O, Laven JS, Eijkemans MJ, Fauser BC. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG. 2006. 113. 1210-1217
    Google Scholar
  • 3 Wehr E, Möller R, Horejsi R, Giuliani A, Kopera D, Schweighofer N, Groselj-Strele A, Pieber TR, Obermayer-Pietsch B. Subcutaneous Adipose Tissue Topography and Metabolic Disturbances in Polycystic Ovary Syndrome. Wien Klin Wochenschr 2009; 121: 262-269
    CrossrefPubMedGoogle Scholar
  • 4 Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, Obermayer-Pietsch B. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol 2009; 161: 575-582
    CrossrefPubMedGoogle Scholar
  • 5 Cho LW, Kilpatrick ES, Keevil BG, Jayagopal V, Coady AM, Rigby AS, Atkin SL. Insulin resistance variability in women with anovulatory and ovulatory polycystic ovary syndrome, and normal controls. Horm Metab Res 2011; 43: 141-145
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352: 1223-1236
    CrossrefPubMedGoogle Scholar
  • 7 Qiu S, Wu C, Lin F, Chen L, Huang Z, Jiang Z. Exercise training improved insulin sensitivity and ovarian morphology in rats with polycystic ovary syndrome. Horm Metab Res. 2009 41. 880-885
    PubMedGoogle Scholar
  • 8 Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle changes in women with polycystic ovary syndrome. Syst Rev . 2011 CD 007506
    PubMedGoogle Scholar
  • 9 Goodarzi MO. Looking for polycystic ovary syndrome genes: rational and best strategy. Semin Reprod Med 2008; 26: 5-13
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Wellcome Trust Case Control Consortium . Genome-wide association study of 14,000 cases of seven common diseases an 3,000 shared controls. Nature 2007; 447: 661-678
    CrossrefPubMedGoogle Scholar
  • 11 Chen ZJ, Zhao H, He L, Shi Y, Qin Y, Shi Y, Li Z, You L, Zhao J, Liu J, Liang X, Zhao X, Zhao J, Sun Y, Zhang B, Jiang H, Zhao D, Bian Y, Gao X, Geng L, Li Y, Zhu D, Sun X, Xu JE, Hao C, Ren CE, Zhang Y, Chen S, Zhang W, Yang A, Yan J, Li Y, Ma J, Zhao Y. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Gen 2010; 43: 45-49
    PubMedGoogle Scholar
  • 12 The Rotterdam ESHRE/ASRM-Sponsored consensus workshop group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19: 41-47
    CrossrefPubMedGoogle Scholar
  • 13 Legro RS, Castracane VD, Kauffman RP. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv 2004; 59: 141-154
    CrossrefPubMedGoogle Scholar
  • 14 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-1470
    CrossrefPubMedGoogle Scholar
  • 15 Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008; 359: 2558-2566
    CrossrefPubMedGoogle Scholar
  • 16 Wehr E, Schweighofer N, Möller R, Giuliani A, Pieber TR, Obermayer-Pietsch B. Association of FTO gene with hyperandrogenemia and metabolic parameters in women with polycystic ovary syndrome. Metabolism 2010; 59: 575-580
    CrossrefPubMedGoogle Scholar
  • 17 Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR, Obermayer-Pietsch B. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol 2011; 164: 741-749
    CrossrefPubMedGoogle Scholar
  • 18 Graupp M, Wehr E, Schweighofer M, Pieber TR, Obermayer-Pietsch B. Association of genetic variants in the two isoforms of the 5-alpha-Reductase SRD5A1 and SRD5A2 in lean patients with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2011; 157: 175-179
    CrossrefPubMedGoogle Scholar
  • 19 Chae SJ, Kim JJ, Choi YM, Hwang KR, Jee BC, Ku SY, Suh CS, Kim SH, Kim JG, Moon SY. Clinical and biochemical characteristics of polycystic ovary syndrome in Korean women. Hum Reprod 2008; 23: 1924-1931
    CrossrefPubMedGoogle Scholar
  • 20 Del Villar K, Miller CA. Down-regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer’s disease brain and hippocampal neurons. Proc Natl Acad Sci USA 2004; 101: 4210-4215
    CrossrefPubMedGoogle Scholar
  • 21 Olszanecka-Glinianowicz M, Banaś M, Zahorska-Markiewicz B, Janowska J, Kocełak P, Madej P, Klimek K. Is the polycystic ovary syndrome associated with chronic inflammation per se?. Eur J Obstet Gynecol Reprod Biol 2007; 133: 197-202
    CrossrefPubMedGoogle Scholar
  • 22 Huang M, Wang H, Li J, Zhou Z, Du Y, Lin M, Sha J. Involvement of ALF in human spermatogenesis and male infertility. Int J Mol Med 2006; 17: 599-604
    PubMedGoogle Scholar
  • 23 Latronico AC, Chai Y, Arnhold IJ, Liu X, Mendonca BB, Segaloff DL. A homozygous microdeletion in helix 7 of the luteinizing hormone receptor associated with familial testicular and ovarian resistance is due to both decreased cell surface expression and impaired effector activation by the cell surface receptor. Mol Endocrinol 1998; 12: 442-450
    CrossrefPubMedGoogle Scholar
  • 24 Toledo SP, Brunner HG, Kraaij R, Post M, Dahia PL, Hayashida CY, Kremer H, Themmen AP. An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46,XX female. J Clin Endocrinol Metab 1996; 81: 3850-3854
    CrossrefPubMedGoogle Scholar
  • 25 Morales AJ, Laughlin GA, Bützow T, Maheshwari H, Baumann G, Yen SS. Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. J Clin Endocrinol Metab 1996; 81: 2854-2864
    CrossrefPubMedGoogle Scholar
  • 26 Arroyo A, Laughlin GA, Morales AJ, Yen SS. Inappropriate gonadotropin secretion in polycystic ovary syndrome: influence of adiposity. J Clin Endocrinol Metab 1997; 82: 3728-3733
    CrossrefPubMedGoogle Scholar
  • 27 Maciel GA, Hayashida SA, da Costa LC, Marcondes JA, da Fonseca AM, Soares Jr JM, Baracat EC. Influence of LH and high-density lipoprotein cholesterol (HDL-C) on metformin response in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2011; 157: 180-184
    CrossrefPubMedGoogle Scholar