Document Type : Review Article
Author
Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
Abstract
Polycystic ovary syndrome (PCOS) is a common infertility disorder, affecting a significant proportion of the global population. This syndrome has been one of the most controversial entities in gynecological endocrinology for many years. Both genes and the environment contribute to PCOS. Obesity, exacerbated by poor dietary choices, and physical inactivity, worsens PCOS in susceptible individuals. PCOS is a complex and heterogeneous disorder characterized by hyperandrogenemia, hyperinsulinemia, insulin resistance, and chronic anovulation. Many candidate genes have been identified to be one of the causes of PCOS. Different studies have been carried out to find the genetic correlation of PCOS. It is essential to carry out such studies that identify the clear cause of PCOS and its genetic association and hormonal disbalance. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants and environmental factors, during either prenatal or postnatal life.
Keywords
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2.
2.Stylianou C, Galli-Tsinopoulou A, Farmakiotis D, Rousso I,
Karamouzis M, Koliakos G, Nousia-Arvanitakis S. Ghrelin and
leptin levels in obese adolescents. Relationship with body fat and
insulin resistance. HORMONES-ATHENS-. 2007 Oct 1;6(4):295.
3.Unluturk U, Harmanci A, Kocaefe C, Yildiz BO. The genetic basis
of the polycystic ovary syndrome: a literature review including
discussion of PPAR-γ. PPAR research. 2007 Oct;2007.
4.Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson
R, McCarthy M. The genetic basis of polycystic ovary syndrome.
Human reproduction (Oxford, England). 1997 Dec 1;12(12):2641-
8.
5.Jahanfar S, Eden JA. Genetic and non-genetic theories on
the etiology of polycystic ovary syndrome. Gynecological
Endocrinology. 1996 Jan 1;10(5):357-64.
6.Adams J, Polson DW, Franks S. Prevalence of polycystic ovaries
in women with anovulation and idiopathic hirsutism. Br Med J
(Clin Res Ed). 1986 Aug 9;293(6543):355-9.
7.FRANKS S. Polycystic ovary syndrome: a changing perspective.
Clinical endocrinology. 1989 Jul;31(1):87-120.
8.Dunaif A, Book CB. Insulin resistance in the polycystic ovary
syndrome. Clinical research in diabetes and obesity. 1997:249-74.
9.Nestler JE. Role of hyperinsulinemia in the pathogenesis of
the polycystic ovary syndrome, and its clinical implications.
InSeminars in reproductive endocrinology 1997 May (Vol. 15,
No. 02, pp. 111-122). Copyright© 1997 by Thieme Medical
Publishers, Inc..
10.Azziz R, Black V, Hines GA, Fox LM, Boots LR. Adrenal
androgen excess in the polycystic ovary syndrome: sensitivity
and responsivity of the hypothalamic-pituitary-adrenal axis.
The Journal of Clinical Endocrinology & Metabolism. 1998 Jul
1;83(7):2317-23.
11.FAUSER BC, PACHE TD, LAMBERTS SW, HOP WC, DE
JONG FH, DAHL KD. Serum bioactive and immunoreactive
luteinizing hormone and follicle-stimulating hormone levels
in women with cycle abnormalities, with or without polycystic
ovarian disease. The Journal of Clinical Endocrinology &
Metabolism. 1991 Oct 1;73(4):811-7.
12.DIAMANTI‐KANDARAKIS EV. The Polycystic Ovary
Syndrome Pathogenesis, Metabolic Implications, and Therapeutic
Approach. Annals of the New York Academy of Sciences. 1997
Jun;816(1):177-93.
13.silchorozidou T, Overton C, Conway GS. The pathophysiology
of polycystic ovary syndrome. Clinical endocrinology. 2004
Jan;60(1):1-7.
14.REDDY¹ KR, N¹ DM, LATHA¹ KP, R¹ SS. Polycystic ovary
syndrome: role of aromatase gene variants in south Indian women.
15.Strachan T, Read AP. Instability of the human genome: mutation
and DNA repair. Human Molecular Genetics. 1999;2:209-17.
16.Abbott D, Dumesic D, Franks S. Developmental origin of
polycystic ovary syndrome. J. Endocrinol.(in the press). 2006.
17.Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the
polycystic ovary syndrome revisited: an update on mechanisms
and implications. Endocrine reviews. 2012 Dec 1;33(6):981-1030.
18.Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS)
and genetic predisposition: A review article. European journal of
obstetrics & gynecology and reproductive biology: X. 2019 Jul
1;3:100060.
19.Helvaci N, Karabulut E, Demir AU, Yildiz BO. Polycystic ovary
syndrome and the risk of obstructive sleep apnea: a meta-analysis
and review of the literature. Endocrine Connections. 2017 Oct
1;6(7):437-45.
20.Legro RS, Driscoll D, Strauss JF, Fox J, Dunaif A. Evidence
for a genetic basis for hyperandrogenemia in polycystic ovary
syndrome. Proceedings of the National Academy of Sciences.
1998 Dec 8;95(25):14956-60.
21.Franks S, McCarthy M. Genetics of ovarian disorders: polycystic
ovary syndrome. Reviews in Endocrine and Metabolic Disorders.
2004 Mar;5(1):69-76.
22.Franks S, Gharani N, Waterworth D, Batty S, White D,
Williamson R, McCarthy M. The genetic basis of polycystic
ovary syndrome. Human reproduction (Oxford, England). 1997
Dec 1;12(12):2641-8.
23.Gharani N, Waterworth DM, Batty S, White D, Gilling-Smith C,
Conway GS, McCarthy M, Franks S, Williamson R. Association
of the steroid synthesis gene CYP11a with polycystic ovary
syndrome and hyperandrogenism. Human Molecular Genetics.
1997 Mar 1;6(3):397-402.
24.Franks S, Gilling-Smith C, Gharani N, McCarthy M. Pathogenesis
of polycystic ovary syndrome: evidence for a genetically
determined disorder of ovarian androgen production. Human
fertility. 2000 Jan 1;3(2):77-9.
25.Diamanti-Kandarakis E, Bartzis MI, Bergiele AT, Tsianateli TC,
Kouli CR. Microsatellite polymorphism (tttta) n at− 528 base
pairs of gene CYP11α influences hyperandrogenemia in patients
with polycystic ovary syndrome. Fertility and Sterility. 2000 Apr
1;73(4):735-41.
26.Wang Y, Wu X, Cao Y, Yi L, Chen J. A microsatellite
polymorphism (tttta) n in the promoter of the CYP11a gene in
Chinese women with polycystic ovary syndrome. Fertility and
sterility. 2006 Jul 1;86(1):223-6.
27.Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS)
and genetic predisposition: A review article. European journal of
obstetrics & gynecology and reproductive biology: X. 2019 Jul
1;3:100060.
28.Matteson KJ, Picado-Leonard J, CHUNG BC, Mohandas TK,
Miller WL. ASSIGNMENT OF THE GENE FOR ADRENAL
P450cl7 (STEROID 17α-HYDR0XYLASE⁄ 17, 20 LYASE)
TO HUMAN CHROMOSOME 10. The Journal of Clinical
Endocrinology & Metabolism. 1986 Sep 1;63(3):789-91.
29.Rosenfield RL, Barnes RB, Jose’F C, Lucky AW. Dysregulation
of cytochrome P450c17α as the cause of polycystic ovarian
syndrome. Fertility and sterility. 1990 May 1;53(5):785-91.
30.Wickenheisser JK, Quinn PG, Nelson VL, Legro RS, Strauss III
JF, McAllister JM. Differential activity of the cytochrome P450
17α-hydroxylase and steroidogenic acute regulatory protein gene
promoters in normal and polycystic ovary syndrome theca cells.
The Journal of Clinical Endocrinology & Metabolism. 2000 Jun
1;85(6):2304-11.
31.Echiburú B, Pérez-Bravo F, Maliqueo M, Sánchez F, Crisosto N,
Sir-Petermann T. Polymorphism T→ C (− 34 base pairs) of gene
CYP17 promoter in women with polycystic ovary syndrome is
associated with increased body weight and insulin resistance: a
preliminary study. Metabolism. 2008 Dec 1;57(12):1765-71.
32.Lüscher TF, Oemar BS, Boulanger CM, Hahn AW. Molecular and
cellular biology of endothelin and its receptors—Part II. Journal
of hypertension. 1993 Feb 1;11(2):121-6.
33.Urbanek M. The genetics of the polycystic ovary syndrome.
Nature clinical practice Endocrinology & metabolism. 2007
Feb;3(2):103-11.
34.Mifsud A, Ramirez S, Yong EL. Androgen receptor gene CAG
trinucleotide repeats in anovulatory infertility and polycystic
ovaries. The Journal of Clinical Endocrinology & Metabolism.
2000 Sep 1;85(9):3484-8.
35.Urbanek M, Wu X, Vickery KR, Kao LC, Christenson LK,
Schneyer A, Legro RS, Driscoll DA, Strauss III JF, Dunaif A,
Spielman RS. Allelic variants of the follistatin gene in polycystic
ovary syndrome. The Journal of Clinical Endocrinology &
Metabolism. 2000 Dec 1;85(12):4455-61.
36.Berube D, Seralini GE, Gagne R, Hammond GL. Localization
of the human sex hormone-binding globulin gene (SHBG) to the
short arm of chromosome 17 (17p12→ p13). Cytogenetic and
Genome Research. 1990;54(1-2):65-7.
endometrial carcinoma. The lancet. 2003 May 24;361(9371):1810-
2.
2.Stylianou C, Galli-Tsinopoulou A, Farmakiotis D, Rousso I,
Karamouzis M, Koliakos G, Nousia-Arvanitakis S. Ghrelin and
leptin levels in obese adolescents. Relationship with body fat and
insulin resistance. HORMONES-ATHENS-. 2007 Oct 1;6(4):295.
3.Unluturk U, Harmanci A, Kocaefe C, Yildiz BO. The genetic basis
of the polycystic ovary syndrome: a literature review including
discussion of PPAR-γ. PPAR research. 2007 Oct;2007.
4.Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson
R, McCarthy M. The genetic basis of polycystic ovary syndrome.
Human reproduction (Oxford, England). 1997 Dec 1;12(12):2641-
8.
5.Jahanfar S, Eden JA. Genetic and non-genetic theories on
the etiology of polycystic ovary syndrome. Gynecological
Endocrinology. 1996 Jan 1;10(5):357-64.
6.Adams J, Polson DW, Franks S. Prevalence of polycystic ovaries
in women with anovulation and idiopathic hirsutism. Br Med J
(Clin Res Ed). 1986 Aug 9;293(6543):355-9.
7.FRANKS S. Polycystic ovary syndrome: a changing perspective.
Clinical endocrinology. 1989 Jul;31(1):87-120.
8.Dunaif A, Book CB. Insulin resistance in the polycystic ovary
syndrome. Clinical research in diabetes and obesity. 1997:249-74.
9.Nestler JE. Role of hyperinsulinemia in the pathogenesis of
the polycystic ovary syndrome, and its clinical implications.
InSeminars in reproductive endocrinology 1997 May (Vol. 15,
No. 02, pp. 111-122). Copyright© 1997 by Thieme Medical
Publishers, Inc..
10.Azziz R, Black V, Hines GA, Fox LM, Boots LR. Adrenal
androgen excess in the polycystic ovary syndrome: sensitivity
and responsivity of the hypothalamic-pituitary-adrenal axis.
The Journal of Clinical Endocrinology & Metabolism. 1998 Jul
1;83(7):2317-23.
11.FAUSER BC, PACHE TD, LAMBERTS SW, HOP WC, DE
JONG FH, DAHL KD. Serum bioactive and immunoreactive
luteinizing hormone and follicle-stimulating hormone levels
in women with cycle abnormalities, with or without polycystic
ovarian disease. The Journal of Clinical Endocrinology &
Metabolism. 1991 Oct 1;73(4):811-7.
12.DIAMANTI‐KANDARAKIS EV. The Polycystic Ovary
Syndrome Pathogenesis, Metabolic Implications, and Therapeutic
Approach. Annals of the New York Academy of Sciences. 1997
Jun;816(1):177-93.
13.silchorozidou T, Overton C, Conway GS. The pathophysiology
of polycystic ovary syndrome. Clinical endocrinology. 2004
Jan;60(1):1-7.
14.REDDY¹ KR, N¹ DM, LATHA¹ KP, R¹ SS. Polycystic ovary
syndrome: role of aromatase gene variants in south Indian women.
15.Strachan T, Read AP. Instability of the human genome: mutation
and DNA repair. Human Molecular Genetics. 1999;2:209-17.
16.Abbott D, Dumesic D, Franks S. Developmental origin of
polycystic ovary syndrome. J. Endocrinol.(in the press). 2006.
17.Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the
polycystic ovary syndrome revisited: an update on mechanisms
and implications. Endocrine reviews. 2012 Dec 1;33(6):981-1030.
18.Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS)
and genetic predisposition: A review article. European journal of
obstetrics & gynecology and reproductive biology: X. 2019 Jul
1;3:100060.
19.Helvaci N, Karabulut E, Demir AU, Yildiz BO. Polycystic ovary
syndrome and the risk of obstructive sleep apnea: a meta-analysis
and review of the literature. Endocrine Connections. 2017 Oct
1;6(7):437-45.
20.Legro RS, Driscoll D, Strauss JF, Fox J, Dunaif A. Evidence
for a genetic basis for hyperandrogenemia in polycystic ovary
syndrome. Proceedings of the National Academy of Sciences.
1998 Dec 8;95(25):14956-60.
21.Franks S, McCarthy M. Genetics of ovarian disorders: polycystic
ovary syndrome. Reviews in Endocrine and Metabolic Disorders.
2004 Mar;5(1):69-76.
22.Franks S, Gharani N, Waterworth D, Batty S, White D,
Williamson R, McCarthy M. The genetic basis of polycystic
ovary syndrome. Human reproduction (Oxford, England). 1997
Dec 1;12(12):2641-8.
23.Gharani N, Waterworth DM, Batty S, White D, Gilling-Smith C,
Conway GS, McCarthy M, Franks S, Williamson R. Association
of the steroid synthesis gene CYP11a with polycystic ovary
syndrome and hyperandrogenism. Human Molecular Genetics.
1997 Mar 1;6(3):397-402.
24.Franks S, Gilling-Smith C, Gharani N, McCarthy M. Pathogenesis
of polycystic ovary syndrome: evidence for a genetically
determined disorder of ovarian androgen production. Human
fertility. 2000 Jan 1;3(2):77-9.
25.Diamanti-Kandarakis E, Bartzis MI, Bergiele AT, Tsianateli TC,
Kouli CR. Microsatellite polymorphism (tttta) n at− 528 base
pairs of gene CYP11α influences hyperandrogenemia in patients
with polycystic ovary syndrome. Fertility and Sterility. 2000 Apr
1;73(4):735-41.
26.Wang Y, Wu X, Cao Y, Yi L, Chen J. A microsatellite
polymorphism (tttta) n in the promoter of the CYP11a gene in
Chinese women with polycystic ovary syndrome. Fertility and
sterility. 2006 Jul 1;86(1):223-6.
27.Ajmal N, Khan SZ, Shaikh R. Polycystic ovary syndrome (PCOS)
and genetic predisposition: A review article. European journal of
obstetrics & gynecology and reproductive biology: X. 2019 Jul
1;3:100060.
28.Matteson KJ, Picado-Leonard J, CHUNG BC, Mohandas TK,
Miller WL. ASSIGNMENT OF THE GENE FOR ADRENAL
P450cl7 (STEROID 17α-HYDR0XYLASE⁄ 17, 20 LYASE)
TO HUMAN CHROMOSOME 10. The Journal of Clinical
Endocrinology & Metabolism. 1986 Sep 1;63(3):789-91.
29.Rosenfield RL, Barnes RB, Jose’F C, Lucky AW. Dysregulation
of cytochrome P450c17α as the cause of polycystic ovarian
syndrome. Fertility and sterility. 1990 May 1;53(5):785-91.
30.Wickenheisser JK, Quinn PG, Nelson VL, Legro RS, Strauss III
JF, McAllister JM. Differential activity of the cytochrome P450
17α-hydroxylase and steroidogenic acute regulatory protein gene
promoters in normal and polycystic ovary syndrome theca cells.
The Journal of Clinical Endocrinology & Metabolism. 2000 Jun
1;85(6):2304-11.
31.Echiburú B, Pérez-Bravo F, Maliqueo M, Sánchez F, Crisosto N,
Sir-Petermann T. Polymorphism T→ C (− 34 base pairs) of gene
CYP17 promoter in women with polycystic ovary syndrome is
associated with increased body weight and insulin resistance: a
preliminary study. Metabolism. 2008 Dec 1;57(12):1765-71.
32.Lüscher TF, Oemar BS, Boulanger CM, Hahn AW. Molecular and
cellular biology of endothelin and its receptors—Part II. Journal
of hypertension. 1993 Feb 1;11(2):121-6.
33.Urbanek M. The genetics of the polycystic ovary syndrome.
Nature clinical practice Endocrinology & metabolism. 2007
Feb;3(2):103-11.
34.Mifsud A, Ramirez S, Yong EL. Androgen receptor gene CAG
trinucleotide repeats in anovulatory infertility and polycystic
ovaries. The Journal of Clinical Endocrinology & Metabolism.
2000 Sep 1;85(9):3484-8.
35.Urbanek M, Wu X, Vickery KR, Kao LC, Christenson LK,
Schneyer A, Legro RS, Driscoll DA, Strauss III JF, Dunaif A,
Spielman RS. Allelic variants of the follistatin gene in polycystic
ovary syndrome. The Journal of Clinical Endocrinology &
Metabolism. 2000 Dec 1;85(12):4455-61.
36.Berube D, Seralini GE, Gagne R, Hammond GL. Localization
of the human sex hormone-binding globulin gene (SHBG) to the
short arm of chromosome 17 (17p12→ p13). Cytogenetic and
Genome Research. 1990;54(1-2):65-7.
37.Hogeveen KN, Cousin P, Pugeat M, Dewailly D, Soudan B,
Hammond GL. Human sex hormone–binding globulin variants
associated with hyperandrogenism and ovarian dysfunction. The
Journal of clinical investigation. 2002 Apr 1;109(7):973-81.
38.Hammond GL. Molecular properties of corticosteroid binding
globulin and the sex-steroid binding proteins. Endocrine reviews.
1990 Feb 1;11(1):65-79.
39.Wickham III EP, Ewens KG, Legro RS, Dunaif A, Nestler JE,
Strauss III JF. Polymorphisms in the SHBG gene influence
serum SHBG levels in women with polycystic ovary syndrome.
The Journal of Clinical Endocrinology & Metabolism. 2011 Apr
1;96(4):E719-27.
40.Nardo LG, Patchava S, Laing I. Polycystic ovary syndrome:
pathophysiology, molecular aspects and clinical implications.
Panminerva medica. 2008 Dec 1;50(4):267-78.
41.Munir I, Yen HW, Geller DH, Torbati D, Bierden RM, Weitsman
SR, Agarwal SK, Magoffin DA. Insulin augmentation of
17α-hydroxylase activity is mediated by phosphatidyl inositol
3-kinase but not extracellular signal-regulated kinase-1/2 in human
ovarian theca cells. Endocrinology. 2004 Jan 1;145(1):175-83.
42.Bennett ST, Lucassen AM, Gough SC, Powell EE, Undlien DE,
Pritchard LE, Merriman ME, Kawaguchi Y, Dronsfield MJ, Pociot
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is determined by tandem repeat variation at the insulin gene
minisatellite locus. Nature genetics. 1995 Mar;9(3):284-92.
43.Waterworth DM, Bennett ST, Gharani N, McCarthy MI, Hague
S, Batty S, Conway GS, White D, Todd JA, Franks S, Williamson
R. Linkage and association of insulin gene VNTR regulatory
polymorphism with polycystic ovary syndrome. The Lancet. 1997
Apr 5;349(9057):986-90.
44.Goldfine ID. The insulin receptor: molecular biology and
transmembrane signaling. Endocrine Reviews. 1987 Aug
1;8(3):235-55.
45.Sorbara LR, Tang Z, Cama A, Xia J, Schenker E, Kohanski
RA, Poretsky L, Koller E, Taylor SI, Dunaif A. Absence of
insulin receptor gene mutations in three insulin-resistant women
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1;43(12):1568-74.
46.Urbanek M, Woodroffe A, Ewens KG, Diamanti-Kandarakis E,
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The Journal of Clinical Endocrinology & Metabolism. 2005 Dec
1;90(12):6623-9.
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receptor gene in a patient with insulin resistance, acanthosis
nigricans, and the polycystic ovary syndrome (type A insulin
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2012 Oct;55(10):2636-45.
50.Rizwan S, Ghazanvi S, Rasheed N, Ullah MI. Association of FTO
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Ovarian Syndrome in Pakistani Women. J Med Res Biol Stud 1:
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1998 Apr;43(4):446-51.
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associated with hyperandrogenism and ovarian dysfunction. The
Journal of clinical investigation. 2002 Apr 1;109(7):973-81.
38.Hammond GL. Molecular properties of corticosteroid binding
globulin and the sex-steroid binding proteins. Endocrine reviews.
1990 Feb 1;11(1):65-79.
39.Wickham III EP, Ewens KG, Legro RS, Dunaif A, Nestler JE,
Strauss III JF. Polymorphisms in the SHBG gene influence
serum SHBG levels in women with polycystic ovary syndrome.
The Journal of Clinical Endocrinology & Metabolism. 2011 Apr
1;96(4):E719-27.
40.Nardo LG, Patchava S, Laing I. Polycystic ovary syndrome:
pathophysiology, molecular aspects and clinical implications.
Panminerva medica. 2008 Dec 1;50(4):267-78.
41.Munir I, Yen HW, Geller DH, Torbati D, Bierden RM, Weitsman
SR, Agarwal SK, Magoffin DA. Insulin augmentation of
17α-hydroxylase activity is mediated by phosphatidyl inositol
3-kinase but not extracellular signal-regulated kinase-1/2 in human
ovarian theca cells. Endocrinology. 2004 Jan 1;145(1):175-83.
42.Bennett ST, Lucassen AM, Gough SC, Powell EE, Undlien DE,
Pritchard LE, Merriman ME, Kawaguchi Y, Dronsfield MJ, Pociot
F, Nerup J. Susceptibility to human type 1 diabetes at IDDM2
is determined by tandem repeat variation at the insulin gene
minisatellite locus. Nature genetics. 1995 Mar;9(3):284-92.
43.Waterworth DM, Bennett ST, Gharani N, McCarthy MI, Hague
S, Batty S, Conway GS, White D, Todd JA, Franks S, Williamson
R. Linkage and association of insulin gene VNTR regulatory
polymorphism with polycystic ovary syndrome. The Lancet. 1997
Apr 5;349(9057):986-90.
44.Goldfine ID. The insulin receptor: molecular biology and
transmembrane signaling. Endocrine Reviews. 1987 Aug
1;8(3):235-55.
45.Sorbara LR, Tang Z, Cama A, Xia J, Schenker E, Kohanski
RA, Poretsky L, Koller E, Taylor SI, Dunaif A. Absence of
insulin receptor gene mutations in three insulin-resistant women
with the polycystic ovary syndrome. Metabolism. 1994 Dec
1;43(12):1568-74.
46.Urbanek M, Woodroffe A, Ewens KG, Diamanti-Kandarakis E,
Legro RS, Strauss Iii JF, Dunaif A, Spielman RS. Candidate gene
region for polycystic ovary syndrome on chromosome 19p13. 2.
The Journal of Clinical Endocrinology & Metabolism. 2005 Dec
1;90(12):6623-9.
47.Moller DE, Flier JS. Detection of an alteration in the insulin-
receptor gene in a patient with insulin resistance, acanthosis
nigricans, and the polycystic ovary syndrome (type A insulin
resistance). New England Journal of Medicine. 1988 Dec
8;319(23):1526-9.
48.Siegel S, Futterweit W, Davies TF, Concepcion ES, Greenberg
DA, Villanueva R, Tomer Y. AC/T single nucleotide polymorphism
at the tyrosine kinase domain of the insulin receptor gene is
associated with polycystic ovary syndrome. Fertility and sterility.
2002 Dec 1;78(6):1240-3.
49.Wojciechowski P, Lipowska A, Rys P, Ewens KG, Franks S, Tan
S, Lerchbaum E, Vcelak J, Attaoua R, Straczkowski M, Azziz R.
Impact of FTO genotypes on BMI and weight in polycystic ovary
syndrome: a systematic review and meta-analysis. Diabetologia.
2012 Oct;55(10):2636-45.
50.Rizwan S, Ghazanvi S, Rasheed N, Ullah MI. Association of FTO
Common RS9939609 Polymor-phism with Obesity and Polycystic
Ovarian Syndrome in Pakistani Women. J Med Res Biol Stud 1:
101 Abstract Keywords: Polycystic Ovarian Syndrome. 2018.
51.Isojärvi JI, Rättyä J, Myllylä VV, Knip M, Koivunen R, Pakarinen
AJ, Tekay A, Tapanainen JS. Valproate, lamotrigine, and insulin‐
mediated risks in women with epilepsy. Annals of neurology.
1998 Apr;43(4):446-51.
52.Crave JC, Fimbel S, Lejeune H, Cugnardey NA, Dechaud H,
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