Table 2.

Summary of the studies of candidate genes in PCOS.

Gene	Locus/variant	Subjects/phenotypic trait	(a) Assoc.	References
Genes involved in ovarian and adrenal steroidogenesis
CYP11a	(tttta)n	PCOS/	Yes	Gharani et al. [29]
		hyperandrogenemia
		PCOS/	Yes	Wang et al. [31]
		body mass index
		PCOS/	Yes	Diamanti-Kandarakis et al. [30]
		hyperandrogenemia
	D15S519	PCOS/	No	Urbanek et al. [35]
	D15S520	hyperandrogenemia
	(tttta)n	Hirsutism/	No	San Millán et al. [36]
		hyperandrogenism
	(tttta)n	PCOS/	No	Tan et al. [33, 34]
		hyperandrogenemia
	D15S520,1500 bp to D15S520	PCOS, (b) PCO/	No	Gaasenbeek et al. [32]
		testosterone levels
CYP21	Heterozygosity for CYP21 mutations	Premature pubarche/	Yes	Witchel et al. [39]
		hyperandrogenism
		Hyperandrogenism	Yes	Witchel et al. [40]
		Hirsutism/	No	Escobar-Morreale et al. [41]
		origin of androgen excess
		Hirsutism, PCOS/	No	Glintborg et al. [42]
		adrenal hyperresponsiveness
		PCOS/	No	Witchel et al. [43]
		hyperandrogenemia
CYP17	−34T/C (c) SNP	PCOS	Yes	Carey et al. [52]
		PCOS/	Yes	Diamanti-Kandarakis et al. [53]
		hyperandrogenemia
		PCOS/	No	Gharani et al. [54]
		hyperandrogenemia
		PCOS/	No	Techatraisak et al. [55]
		hyperandrogenemia
		PCOS/	No	Marszalek et al. [57]
		hormone profile
	Mutation scanning/	Mild	No	Witchel et al. [56]
	no mutation	hyperandrogenism
	D10S192	PCOS	No	Urbanek et al. [35]
	T/C substitution in the 5′ (d) PR	PCOS/	No	Kahsar-Miller et al. [58]
		(e) DHEAS levels
CYP19	CYP19	PCOS	No	Urbanek et al. [35]
	(tttta)n/D15S103	PCOS	No	Gharani et al. [29]
	Aromatase SNP_50 genotype Aromatase distal promoter region variation	PCOS symptom score testosterone concentrations	Yes	Petry et al. [74, 75]
Genes involved in steroid hormone effects
AR	AR	PCOS	No	Urbanek et al. [35]
SHBG gene	AR (CAG)n	PCOS/infertile and	No	Mifsud et al. [83]
		fertile women
		PCOS/infertility	Yes	Hickey et al. [84]
		PCOS/ (f) BMI,	No	Jääskeläinen et al. [85]
		testosterone levels
	(TAAAA)n	PCOS/SHBG levels	Yes	Xita et al. [90]
	Asp327Asn	Hirsutism/SHBG levels	Yes	Cousin et al. [91]
	D17S1353	PCOS	No	Urbanek et al. [35]
Genes involved in gonadotropin action and regulation
LHβ	Trp8Arg; Ilg15Thr	PCOS/higher frequency of	Yes	Rajkhowa et al. [98]
		the SNPs in obese PCOS
		PCOS/lower frequency of	Yes	Tapanainen et al. [99]
		the SNPs in obese PCOS
		Menstrual disorders	No	Ramanujam et al. [100]
	Ser102 Gly	Menstrual disorders	Yes	Ramanujam et al. [100]
	Trp8Arg; Ilg15Thr	PCOS	No	Elter et al. [101]
	Several SNPs	Ovulatory disorders	Yes	Takahashi et al. [103]
		including PCOS
Follistatin gene	D5S474	PCOS	Yes	Urbanek et al. [35]
	D5S623
	D5S822
	Mutation scanning/	PCOS	No	Urbanek et al. [110]
	variants at 17 sites
	Mutation scanning/	PCOS	No	Liao et al. [111]
	no mutation
	Mutation scanning/	PCOS/hormone profile	No	Calvo et al. [112]
	no mutation except
	G951A (silent mutation)
Genes involved in insulin action and secretion
INS	INS VNRT	PCOS/premature male	Yes	Waterworth et al. [123]
		pattern baldness
		PCOS	Yes	Eaves et al. [124]
		PCOS/insulin resistance	Yes	Michelmore et al. [125]
		and hyperandrogenemia
		PCOS/	No	Urbanek et al. [35]
		hyperandrogenemia
		Hyperandrogenemia	No	Calvo et al. [126]
		PCOS/insulin	No	Vankova et al. [127]
		secretion and action
		PCOS; PCO;	No	Powell et al. [129]
		testosterone level
INSR	Mutation scanning	PCOS/insulin resistance	No	Talbot et al. [133]
	D19S884	PCOS	Border	Urbanek et al. [35]
		PCOS	Yes	Tucci et al. [134]
		PCOS	No	Villuendas et al. [135]
		PCOS	Yes	Urbanek et al. [136]
	C10923T	PCOS/lean subjects	Yes	Siegal et al. [137]
IRS	IRS1	PCOS	No	Urbanek et al. [35]
	Gly972Arg (IRS1)	PCOS	Yes	Sir-Petermann et al. [142]
	Gly972Arg (IRS1)	PCOS/insulin resistance	Yes	El-Mkadem et al. [143]
	Gly1057Asp(IRS2)
IRS	Gly972Arg (IRS1)	PCOS/insulin and glucose levels	No	Ehrmann et al. [144]
	Gly972Arg (IRS1)	PCOS/glucose homeostasis	No	Villuendas et al. [145]
	Gly1057Asp(IRS2)
	Gly972Arg (IRS1)	PCOS/insulin resistance, and obesity	Yes	Dilek et al. [146]
		PCOS/insulin resistance, hormone profile, and metformin effects	Yes	Ertunc et al. [147]
CAPN10	UCSNP-19, -43, and -63	PCOS/insulin levels	Yes	Ehrmann et al. [152]
	UCSNP-19, -43, -44, and -63	PCOS	Yes	Gonzales et al. [153, 154]
		PCOS/insulin levels	No	Haddad et al. [155]
	UCSNP-43	Hirsutism/hirsutism score	Yes	Escobar-Morreale et al. [156]
	UCSNP-44	Hirsutism/PCOS, idiopathic hirsutism, and hyperandrogenism	No	Escobar-Morreale et al. [156]
	UCSNP-45	Hirsutism/idiopathic hirsutism	Yes	Escobar-Morreale et al. [156]
Genes involved in energy homeostasis
Leptin gene & Leptin receptor	Mutation scanning of the leptin gene; polymorphism in leptin receptor gene	PCOS/obesity	No	Oksanen et al. [158]
Adiponectin gene	T45G in exon 2	PCOS	No	San Millán et al. [163]
	G276T in intron 2
	T45G in exon 2	PCOS	No	Panidis et al. [164]
	T45G in exon 2	PCOS	No	Xita et al. [165]
	G276T in intron 2	PCOS	No	Escobar-Morreale et al. [166]
Genes involved in chronic inflammation
TNF-α	−308 G/A	PCOS	No	Milner et al. [185]
		PCOS	No	Mao et al. [186]
		PCOS	No	Korhonen et al. [187]
TNFR2 gene	Met196Arg	PCOS/	Yes	Peral et al. [188]
		hyperandrogenism
IL-6	−174 G/C	PCOS	Yes	Mohlig et al. [189]
IL-6 signal	Gly148Arg	PCOS/	Yes	Escobar-Morreale et al. [190]
transducer gp 130		hyperandrogenism
IL-6 receptor-α	CA repeats	PCOS/obesity, and Hyperandrogenism	Yes	Escobar-Morreale et al. [190]

^(a)Assoc.: association.

^(b)PCO: polycystic ovaries.

^(c)SNP: single nucleotide polymorphism.

^(d)PR: promoter region.

^(e)DHEAS: dehydroepiandrosterone sulfate.

^(f)BMI: body mass index.