The role of genes in the polycystic ovary syndrome: Predisposition and mechanisms

References

• Carmina E, Lobo R A. Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab 1999; 84: 1897–1899
   PubMed Web of Science ®Google Scholar
• Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18: 774–800
   PubMed Web of Science ®Google Scholar
• Stein I F, Leventhal L M. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29: 181–191
   Google Scholar
• Zawadzki J K, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. Polycystic ovary syndrome, A Dunaif, J R Givens, F P Haseltine, G R Merriam. Blackwell Scientific Publications, Boston 1992; 377–384
   Google Scholar
• The Rotterdam ESHRE/ASRM – Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Fertil Steril 2004; 81: 19–25
   Web of Science ®Google Scholar
• Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale H F, Futterweit W, Janssen O E, Legro R S, Norman R J, Taylor A E, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006; 91: 4237–4245
   PubMed Web of Science ®Google Scholar
• Azziz R. The Polycystic ovary syndrome: current concepts on pathogenesis and clinical care. Springer. Springer Science and Business Media, New York 2007; 1–15, 29–42
   Google Scholar
• Kahsar-Miller M D, Nixon C, Boots L R, Go R C, Azziz R. Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil Steril 2001; 75: 53–58
   PubMed Web of Science ®Google Scholar
• Ferriman D, Purdie A W. The inheritance of polycystic ovarian disease and a possible relationship to premature balding. Clin Endocrinol (Oxf) 1979; 11: 291–300
   PubMed Web of Science ®Google Scholar
• Lunde O, Magnus P, Sandvik L, Hoglo S. Familial clustering in the polycystic ovarian syndrome. Gynecol Obstet Invest 1989; 28: 23–30
   PubMed Web of Science ®Google Scholar
• Legro R S. Is there a male phenotype in polycystic ovary syndrome families. J Pediatr Endocrinol Metab 2000; 13: 1307–1309
   PubMed Web of Science ®Google Scholar
• Legro R S, Kunselman A R, Demers L, Wang S C, Bentley-Lewis R, Dunaif A. Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 2134–2138
   PubMed Web of Science ®Google Scholar
• Jahanfar S, Eden J A, Warren P, Seppälä M, Nguyen T V. A twin study of polycystic ovary syndrome. Fertil Steril 1995; 63: 478–486
   PubMed Web of Science ®Google Scholar
• Jahanfar S, Eden J A, Nguyen T, Wang X L, Wilcken D E. A twin study of polycystic ovary syndrome and lipids. Gynecol Endocrinol 1997; 11: 111–117
   PubMed Web of Science ®Google Scholar
• Carmina E, Koyama T, Chang L, Stanczyk F Z, Lobo R A. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome. Am J Obstet Gynecol 1992; 167: 1807–1812
   PubMed Web of Science ®Google Scholar
• Dunaif A, Sorbara L, Delson R, Green G. Ethnicity and polycystic ovary syndrome are associated with independent and additive decreases in insulin action in Carribean-Hispanic women. Diabetes 1993; 42: 1462–1468
   PubMed Web of Science ®Google Scholar
• Xita N, Tsatsoulis A. Review: fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical and genetic association studies. J Clin Endocrinol Metab 2006; 91: 1660–1606
   PubMed Web of Science ®Google Scholar
• Escobar-Morreale H F, Luque-Ramirez M, San Millan J L. The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr Rev 2005; 26: 251–282
   PubMed Web of Science ®Google Scholar
• Gambineri A, Vicennati V, Genghini S, Tomassoni F, Pagotto U, Pasquali R, Walker B R. Genetic variation in 11β-Hydroxysteroid Dehydrogenase predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 2295–2302
   PubMed Web of Science ®Google Scholar
• Qin K, Ehrmann D A, Cox N, Refetoff S, Rosenfield R L. Identification of a functional polymorphism of the human type 5 17-β Hydroxysteroid Dehydrogenase gene associated with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 270–276
   PubMed Web of Science ®Google Scholar
• Goodarzi M O, Jones M R, Antoine H J, Pall M, Chen Y D, Azziz R. Nonreplication of the 5 17-β Hydroxysteroid Dehydrogenase gene association with polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93: 300–303
   PubMed Web of Science ®Google Scholar
• Diamanti-Kandarakis E, Bartzis M I, Zapanti E D, Spina G G, Filandra F A, Tsianateli T C, Bergiele A T, Kouli C R. Polymorphism T→C (-34 bp) of gene CYP17 promoter in Greek patients with polycystic ovary syndrome. Fertil Steril 1999; 71: 431–435
   PubMed Web of Science ®Google Scholar
• Hickey T, Chandy A, Norman R J. The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 161–165
   PubMed Web of Science ®Google Scholar
• Ferk P, Teran N, Gersak K. The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome. Hum Reprod 2007; 22: 1031–1036
   PubMed Web of Science ®Google Scholar
• Goodarzi M O, Shah N A, Antoine H J, Pall M, Guo X, Azziz R. Variants in the 5α-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women. J Clin Endocrinol Metab 2006; 91: 4085–4091
   PubMed Web of Science ®Google Scholar
• Kaibe M, Takakuwa K, Murakawa H, Ishii K, Tamura M, Tanaka K. Studies on the human leukocyte antigens in patients with polycystic ovary syndrome in a Japanese population – possible susceptibility of HLA-A11 and -DRB1*0403 to patient population with polycystic ovary syndrome. Am J Reprod Immunol 2006; 55: 301–306
   PubMed Web of Science ®Google Scholar
• Waterworth D M, Bennett S T, Gharani N, McCarthy M I, Hague S, Batty S, Conway G S, White D, Todd J A, Franks S, et al. Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet 1997; 349: 986–990
   PubMed Web of Science ®Google Scholar
• Vanková M, Vrbíková J, Hill M, Cinek O, Bendlová B. Association of insulin gene VNTR polymorphism with polycystic ovary syndrome. Ann N Y Acad Sci 2002; 967: 558–565
   PubMed Web of Science ®Google Scholar
• Conway G S, Avey C, Rumsby G. The tyrosine kinase domain of the insulin receptor gene is normal in women with hyperinsulinaemia and polycystic ovary syndrome. Hum Reprod 1994; 9: 1681–1683
   PubMed Web of Science ®Google Scholar
• Sorbara L R, Tang Z, Cama A, Xia J, Schenker E, Kohanski R A, Poretsky L, Koller E, Taylor S I, Dunaif A. Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome. Metabolism 1994; 43: 1568–1574
   PubMed Web of Science ®Google Scholar
• Dunaif A, Xia J, Book C B, Schenker E, Tang Z. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Invest 1995; 96: 801–810
   PubMed Web of Science ®Google Scholar
• Siegel S, Futterweit W, Davies T F, Concepcion E S, Greenberg D A, Villanueva R, Tomer Y. A C/T single nucleotide polymorphism at the tyrosine kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome. Fertil Steril 2002; 78: 1240–1243
   PubMed Web of Science ®Google Scholar
• Ehrmann D A, Tang X, Yoshiuchi I, Cox N J, Bell G I. Relationship of insulin receptor substrate-1 and -2 genotypes to phenotypic features of polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 4297–4300
   PubMed Web of Science ®Google Scholar
• Giudice L C. Growth factor action on ovarian function in polycystic ovary syndrome. Endocrinol Metab Clin North Am 1999; 28: 325–339
   PubMed Web of Science ®Google Scholar
• Hara M, Alcoser S Y, Qaadir A, Beiswenger K K, Cox N J, Ehrmann D A. Insulin resistance is attenuated in women with polycystic ovary syndrome with the Pro12Ala polymorphism in the PPAR-γ gene. J Clin Endocrinol Metab 2002; 87: 772–775
   PubMed Web of Science ®Google Scholar
• Orio F, Jr, Matarese G, Di Biase S, Palomba S, Labella D, Sanna V, Savastano S, Zullo F, Colao A, Lombardi G. Exon 6 and 2 peroxisome proliferator-activated receptor-γ polymorphisms in the polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 5887–5892
   PubMed Web of Science ®Google Scholar
• Fenkci I V, Serteser M, Fenkci S, Kose S. Paraoxonase levels in women with polycystic ovary syndrome. J Reprod Med 2007; 52: 879–883
   PubMed Web of Science ®Google Scholar
• Ehrmann D A, Schwarz P E, Hara M, Tang X, Horikawa Y, Imperial J, Bell G I, Cox N J. Relationship of Calpain-10 genotype to phenotypic features of polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 1669–1673
   PubMed Web of Science ®Google Scholar
• Escobar-Morreale H F, Peral B, Villuendas G, Calvo R M, Sancho J, San Millán J L. Common single nucleotide polymorphisms in intron 3 of the Calpain-10 gene influene hirsutism. Fertil Steril 2002; 77: 581–587
   PubMed Web of Science ®Google Scholar
• Fernandez-Real J M, Ricart W. Insulin resistance and inflammation in an evolutionary perspective: the contribution of cytokine genotype/phenotype to thriftiness. Diabetologia 1999; 42: 1367–1374
   PubMed Web of Science ®Google Scholar
• Uysal K T, Wiesbrock S M, Hotamisligil G S. Functional analysis of tumor necrosis factor receptors in TNF-a mediated insulin resistance in genetic obesity. Endocrinology 1998; 139: 4832–4838
   PubMed Web of Science ®Google Scholar
• Fernández-Real J M, Vendrell J, Ricart W, Broch M, Gutiérrez C, Casamitjana R, Oriola J, Richart C. Polymorphism of the tumor necrosis factor – alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients. Diabetes Care 2000; 23: 831–837
   PubMed Web of Science ®Google Scholar
• Peral B, San Millán J L, Castello R, Moghetti P, Escobar-Morreale H F. The methionine 196 arginine polymorphism in exon 6 of the TNF receptor 2 gene (TNFRSF1B) is associated with the polycystic ovary syndrome and hyperandrogenism. J Clin Endocrinol Metab 2002; 87: 3977–3983
   PubMed Web of Science ®Google Scholar
• Walch K, Grimm C, Zeillinger R, Huber J C, Nagele F, Hefler L A. A common interleukin-6 gene promoter polymorphism influences the clinical characteristics of women with polycystic ovary syndrome. Fertil Steril 2004; 81: 1638–1641
   PubMed Web of Science ®Google Scholar
• Hassett C, Aicher L, Sidhu J S, Omiecinski C J. Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants. Hum Mol Genet 1994; 3: 421–428
   PubMed Web of Science ®Google Scholar
• Hartsfield J K, Jr, Sutcliffe M J, Everett E T, Hassett C, Omiecinski C J, Saari J A. Assignment of microsomal epoxide hydrolase (EPHX1) to human chromosome 1q42.1 by in situ hybridization. Cytogenet Cell Genet 1998; 83: 44–45
   PubMedGoogle Scholar
• Hippelainen M, Heinonen S. Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are associated with polycystic ovary syndrome. Fertil Steril 2003; 79: 1353–1357
   PubMed Web of Science ®Google Scholar
• Unluturk U, Harmanaci A, Kocaefe C, Yildiz B O. The genetic basis of the polycystic ovary syndrome: a literature review including discussion of PPAR-γ. PPAR Res 2007; 2007: 49109
   PubMed Web of Science ®Google Scholar