Genetics of polycystic ovarian syndrome

Clinical Obstetrics and Gynecology

Volumn 50, Issue 1, 2007, Pages 188-204

  Nam Menke, Marie ^a,c   Strauss, Jerome F ^b  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c VCUHS   (United States)

Author keywords

Association studies; Candidate genes; Complex disorder; Linkage analysis; PCOS; Reproductive medicine; Women's health

Indexed keywords

CALPAIN 10; CYTOCHROME P450; CYTOCHROME P450 11A; CYTOCHROME P450 17; FIBRILLIN; FIBRILLIN 3; FOLLISTATIN; INSULINASE; SEX HORMONE BINDING GLOBULIN; UNCLASSIFIED DRUG;

ANALYTICAL ERROR; ARTICLE; DIAGNOSTIC PROCEDURE; DISEASE CLASSIFICATION; EPIGENETICS; FAMILIAL DISEASE; GENE LINKAGE DISEQUILIBRIUM; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC PREDISPOSITION; GENETIC SCREENING; HUMAN; HUMAN GENETICS; INHERITANCE; OVARY POLYCYSTIC DISEASE; PHENOTYPE; REPRODUCTION; SAMPLE SIZE;

FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENETIC SCREENING; HUMANS; INHERITANCE PATTERNS; LINKAGE (GENETICS); POLYCYSTIC OVARY SYNDROME; SIBLINGS;

EID: 33847120210     PISSN: 00099201     EISSN: None     Source Type: Journal    
DOI: 10.1097/GRF.0b013e3180305f7c     Document Type: Article

References (89)

1. Cooper HE, Spellacy WN, Prem KA, et al. Hereditary factors in the Stein-Leventhal syndrome. Am J Obstet Gynecol. 1968;100:371-387.
2. Ferriman D, Purdie AW. The inheritance of polycystic ovarian disease and a possible relationship to premature balding. Clin Endocrinol (Oxf). 1979;11:291-300.
3. Kahsar-Miller MD, Nixon C, Boots LR, et al. Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil Steril. 2001;75:53-58.
4. Azziz R, Kashar-Miller MD. Family history as a risk factor for the polycystic ovary syndrome. J Pediatr Endocrinol Metab. 2000;13(suppl 5):1303-1306.
5. Lunde O, Magnus P, Sandvik L, et al. Familial clustering in the polycystic ovarian syndrome. Gynecol Obstet Invest. 1989;28:23-30.
6. Givens JR. Familial polycystic ovarian disease. Endocrinol Metab Clin North Am. 1988;17:771-783.
7. Franks S, Gharani N, Waterworth D, et al. The genetic basis of polycystic ovary syndrome. Hum Reprod. 1997;12:2641-2648.
8. Vink JM, Sadrzadeh S, Lambalk CB, et al. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab. 2006;91:2100-2104.
9. Hutton C, Clark F. Polycystic ovarian syndrome in identical twins. Postgrad Med J. 1984;60:64-65.
10. Jahanfar S, Eden JA, Warren P, et al. A twin study of polycystic ovary syndrome. Fertil Steril. 1995;63:478-486.
11. Jahanfar S, Eden JA, Nguyen T, et al. A twin study of polycystic ovary syndrome and lipids. Gynecol Endocrinol. 1997;11:111-117.
12. Legro RS, Driscoll D, Strauss JF III, et al. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci U S A. 1998;95:14956-14960.
13. Hong Y, Gagnon J, Rice T, et al. Familial resemblance for free androgens and androgen glucuronides in sedentary black and white individuals: the HERITAGE Family Study. Health, Risk Factors, Exercise Training and Genetics. J Endocrinol. 2001;170:485-492.
14. Meikle AW, Stringham JD, Bishop DT, et al. Quantitating genetic and nongenetic factors influencing androgen production and clearance rates in men. J Clin Endocrinol Metab. 1988;67:104-109.
15. Harris JA, Vernon PA, Boomsma DI. The heritability of testosterone: a study of Dutch adolescent twins and their parents. Behav Genet. 1998;28:165-171.
16. Urbanek M, Spielman RS. Genetic analysis of candidate genes for the polycystic ovary syndrome. Curr Opin Endocrinol Diabetes. 2002;9:492-501.
17. Haddad L, Evans JC, Gharani N, et al. Variation within the type 2 diabetes susceptibility gene calpain-10 and polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:2606-2610.
18. Seminara SB, Crowley WF Jr. Genetic approaches to unraveling reproductive disorders: examples of bedside to bench research in the genomic era. Endocr Rev. 2002;23:382-392.
19. Lander ES, Schork NJ. Genetic dissection of complex traits. Science. 1994;265:2037-2048.
20. Vink JM, Boomsma DI. Gene finding strategies. Biol Psychol. 2002;61:53-71.
21. Newton-Cheh C, Hirschhorn JN. Genetic association studies of complex traits: design and analysis issues. Mutat Res. 2005;573:54-69.
22. Hirschhorn JN, Lohmueller K, Byrne E, et al. A comprehensive review of genetic association studies. Genet Med. 2002;4:45-61.
23. Crosignani PG, Nicolosi AE. Polycystic ovarian disease: heritability and heterogeneity. Hum Reprod Update. 2001;7:3-7.
24. Carmina E, Koyama T, Chang L, et al. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol. 1992;167:1807-1812.
25. Dunaif A, Sorbara L, Delson R, et al. Ethnicity and polycystic ovary syndrome are associated with independent and additive decreases in insulin action in Caribbean-Hispanic women. Diabetes. 1993;42:1462-1468.
26. Williamson K, Gunn AJ, Johnson N, et al. The impact of ethnicity on the presentation of polycystic ovarian syndrome. Aust N Z J Obstet Gynaecol. 2001;41:202-206.
27. Spielman RS, McGinnis RE, Ewens WJ. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993;52:506-516.
28. Kahn JA, Gordon CM. Polycystic ovary syndrome. Adolesc Med. 1999;10:321-336.
29. Ott J. Association of genetic loci: replication or not, that is the question. Neurology. 2004;63:955-958.
30. Colhoun HM, McKeigue PM, Davey Smith G. Problems of reporting genetic associations with complex outcomes. Lancet. 2003;361:865-872.
31. Reich DE, Goldstein DB. Detecting association in a case-control study while correcting for population stratification. Genet Epidemiol. 2001;20:4-16.
32. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Working Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19-25.
33. Polson DW, Adams J, Wadsworth J, et al. Polycystic ovaries - a common finding in normal women. Lancet. 1988;1:870-872.
34. Farquhar CM, Birdsall M, Manning P, et al. The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women. Aust N Z J Obstet Gynaecol. 1994;34:67-72.
35. Stewart DR, Dombroski B, Urbanek M, et al. Fine Mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity. J Clin Endocrinol Metab. 2006;91:4112-4117.
36. San Millan JL, Corton M, Villuendas G, et al. Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. J Clin Endocrinol Metab. 2004;89:2640-2646.
37. Xita N, Tsatsoulis A, Chatzikyriakidou A, et al. Association of the (TAAAA)n repeat polymorphism in the sex hormone-binding globulin (SHBG) gene with polycystic ovary syndrome and relation to SHBG serum levels. J Clin Endocrinol Metab. 2003;88:5976-5980.
38. Cousin P, Calemard-Michel L, Lejeune H, et al. Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women. J Clin Endocrinol Metab. 2004;89:917-924.
39. UrbanekM, Legro RS, Driscoll DA, et al. Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci U S A. 1999;96:8573-8578.
40. Hogeveen KN, Cousin P, Pugeat M, et al. Human sex hormone-binding globulin variants associated with hyperandrogenism and ovarian dysfunction. J Clin Invest. 2002;109:973-981.
41. Mifsud A, Ramirez S, Yong EL. Androgen receptor gene CAG trinucleotide repeats in anovulatory infertility and polycystic ovaries. J Clin Endocrinol Metab. 2000;85:3484-3488.
42. Hickey T, Chandy A, Norman RJ. 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.
43. Ehrmann DA, Schwarz PE, Hara M, et al. Relationship of calpain-10 genotype to phenotypic features of polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:1669-1673.
44. Gonzalez A, Abril E, Roca A, et al. Comment: CAPN10 alleles are associated with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:3971-3976.
45. Escobar-Morreale HF, San Millan JL, Smith RR, et al. The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations. Fertil Steril. 1999;72:629-638.
46. Witchel SF, Aston CE. The role of heterozygosity for CYP21 in the polycystic ovary syndrome. J Pediatr Endocrinol Metab. 2000;13(suppl 5):1315-1317.
47. Witchel SF, Kahsar-Miller M, Aston CE, et al. Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess. Fertil Steril. 2005;83:371-375.
48. Legro RS, Muhleman DR, Comings DE, et al. A dopamine D3 receptor genotype is associated with hyperandrogenic chronic anovulation and resistant to ovulation induction with clomiphene citrate in female Hispanics. Fertil Steril. 1995;63:779-784.
49. Kahsar-Miller M, Boots LR, Azziz R. Dopamine D3 receptor polymorphism is not associated with the polycystic ovary syndrome. Fertil Steril. 1999;71:436-438.
50. Tong Y, Liao WX, Roy AC, et al. Association of AccI polymorphism in the follicle-stimulating hormone beta gene with polycystic ovary syndrome. Fertil Steril. 2000;74:1233-1236.
51. El Mkadem SA, Lautier C, Macari F, et al. Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome. Diabetes. 2001;50:2164-2168.
52. Heinonen S, Korhonen S, Hippelainen M, et al. Apolipoprotein E alleles in women with polycystic ovary syndrome. Fertil Steril. 2001;75:878-880.
53. Urbanek M, Woodroffe A, Ewens KG, et al. Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2. J Clin Endocrinol Metab. 2005;90:6623-6629.
54. Gharani N, Waterworth DM, Batty S, et al. Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism. Hum Mol Genet. 1997;6:397-402.
55. Diamanti-Kandarakis E, Bartzis MI, Bergiele AT, et al. Microsatellite polymorphism (tttta)(n) at -528 base pairs of gene CYP11alpha influences hyperandrogenemia in patients with polycystic ovary syndrome. Fertil Steril. 2000;73:735-741.
56. Wang Y, Wu X, Cao Y, et al. A microsatellite polymorphism (tttta)n in the promoter of the CYP11a gene in Chinese women with polycystic ovary syndrome. Fertil Steril. 2006;86:223-226.
57. Tucci S, Futterweit W, Concepcion ES, et al. Evidence for association of polycystic ovary syndrome in caucasian women with a marker at the insulin receptor gene locus. J Clin Endocrinol Metab. 2001;86:446-449.
58. Carey AH, Chan KL, Short F, et al. Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol (Oxf). 1993;38:653-658.
59. Gharani N, Waterworth DM, Williamson R, et al. 5′ polymorphism of the CYP17 gene is not associated with serum testosterone levels in women with polycystic ovaries. J Clin Endocrinol Metab. 1996;81:4174.
60. Urbanek M, Wu X, Vickery KR, et al. Allelic variants of the follistatin gene in polycystic ovary syndrome. J Clin Endocrinol Metab. 2000;85:4455-4461.
61. Calvo RM, Villuendas G, Sancho J, et al. Role of the follistatin gene in women with polycystic ovary syndrome. Fertil Steril. 2001;75:1020-1023.
62. Liao WX, Roy AC, Ng SC. Preliminary investigation of follistatin gene mutations in women with polycystic ovary syndrome. Mol Hum Reprod. 2000;6:587-590.
63. Conway GS, Conway E, Walker C, et al. Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome. Clin Endocrinol (Oxf). 1999;51:97-99.
64. Takakura K, Takebayashi K, Wang HQ, et al. Follicle-stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome. Fertil Steril. 2001;75:207-209.
65. Takebayashi K, Takakura K, Wang H, et al. Mutation analysis of the growth differentiation factor-9 and -9B genes in patients with premature ovarian failure and polycystic ovary syndrome. Fertil Steril. 2000;74:976-979.
66. Kahsar-Miller M, Azziz R, Feingold E, et al. A variant of the glucocorticoid receptor gene is not associated with adrenal androgen excess in women with polycystic ovary syndrome. Fertil Steril. 2000;74:1237-1240.
67. Moghrabi N, Hughes IA, Dunaif A, et al. Deleterious missense mutations and silent polymorphism in the human 17beta-hydroxysteroid dehydrogenase 3 gene (HSD17B3). J Clin Endocrinol Metab. 1998;83:2855-2860.
68. Waterworth DM, Bennett ST, Gharani N, et al. Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet. 1997;349:986-990.
69. Tapanainen JS, Koivunen R, Fauser BC, et al. A new contributing factor to polycystic ovary syndrome: the genetic variant of luteinizing hormone. J Clin Endocrinol Metab. 1999;84:1711-1715.
70. Kim NK, Nam YS, Ko JJ, et al. The luteinizing hormone beta-subunit exon 3 (Gly102Ser) gene mutation is rare in Korean women with endometriosis and polycystic ovary syndrome. Fertil Steril. 2001;75:1238-1239.
71. Oksanen L, Tiitinen A, Kaprio J, et al. No evidence for mutations of the leptin or leptin receptor genes in women with polycystic ovary syndrome. Mol Hum Reprod. 2000;6:873-876.
72. Urbanek M, Du Y, Silander K, et al. Variation in resistin gene promoter not associated with polycystic ovary syndrome. Diabetes. 2003;52:214-217.
73. Milner CR, Craig JE, Hussey ND, et al. No association between the -308 polymorphism in the tumour necrosis factor alpha (TNFalpha) promoter region and polycystic ovaries. Mol Hum Reprod. 1999;5:5-9.
74. Talbot JA, Bicknell EJ, Rajkhowa M, et al. Molecular scanning of the insulin receptor gene in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 1996;81:1979-1983.
75. Villuendas G, Escobar-Morreale HF, Tosi F, et al. Association between the D19S884 marker at the insulin receptor gene locus and polycystic ovary syndrome. Fertil Steril. 2003;79:219-220.
76. Hanis CL, Boerwinkle E, Chakraborty R, et al. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat Genet. 1996;13:161-166.
77. Horikawa Y, Oda N, Cox NJ, et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet. 2000;26:163-175.
78. Escobar-Morreale HF, Peral B, Villuendas G, et al. Common single nucleotide polymorphisms in intron 3 of the calpain-10 gene influence hirsutism. Fertil Steril. 2002;77:581-587.
79. Gaasenbeek M, Powell BL, Sovio U, et al. Large-scale analysis of the relationship between CYP11A promoter variation, polycystic ovarian syndrome, and serum testosterone. J Clin Endocrinol Metab. 2004;89:2408-2413.
80. Bennett ST, Lucassen AM, Gough SC, et al. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nat Genet. 1995;9:284-292.
81. McKeigue P, Wild S. Association of insulin gene VNTR polymorphism with polycystic ovary syndrome. Lancet. 1997;349:1771-1772.
82. Michelmore K, Ong K, Mason S, et al. Clinical features in women with polycystic ovaries: relationships to insulin sensitivity, insulin gene VNTR and birth weight. Clin Endocrinol (Oxf). 2001;55:439-446.
83. Calvo RM, Telleria D, Sancho J, et al. Insulin gene variable number of tandem repeats regulatory polymorphism is not associated with hyperandrogenism in Spanish women. Fertil Steril. 2002;77:666-668.
84. Powell BL, Haddad L, Bennett A, et al. Analysis of multiple data sets reveals no association between the insulin gene variable number tandem repeat element and polycystic ovary syndrome or related traits. J Clin Endocrinol Metab. 2005;90:2988-2993.
85. Vankova M, Vrbikova J, Hill M, et al. Association of insulin gene VNTR polymorphism with polycystic ovary syndrome. Ann N Y Acad Sci. 2002;967:558-565.
86. Franks S, McCarthy MI, Hardy K. Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl. 2006;29:278-285; discussion 86-90.
87. 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;91:1660-1666.
88. Hickey TE, Legro RS, Norman RJ. Epigenetic modification of the X chromosome influences susceptibility to polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91:2789-2791.
89. Puck JM, Willard HF. X inactivation in females with X-linked disease. N Engl J Med. 1998;338:325-328.