IRS1: Polycystic Ovarian Syndrome Database

Interactions

STRING	MINT	IntAct
ENSP00000302665	P05019	P05019

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Associated Diseases

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Disease group	Disease Name	References
Cardiovascular Diseases
	Coronary heart disease	28869590
	Arteriosclerosis	10591678
Endocrine System Diseases
	Diabetes Mellitus	8104271, 8723689, 19734900, 28869590, 15688983, 12679424, 10430617, 10206679, 12843189, 10591678
	PCOS	15705377
Neoplasms
	Prostate cancer	15678496
	Liver Cancer	1311924, 23958494
Nutritional and Metabolic Diseases
	Hyperinsulinism	19734900
	Hyperlipidemia	10591678
	Obesity	23954404
	Gluocose Intolerance	19140314, 11679606, 15209769
Psychiatric/Brain disorders
Psychiatric/Brain disorders	Obstructive Sleep Apnea	27509181, 17075427

References

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PubMed ID	Associated gene/s	Associated condition	Genetic Mutation	Diagnostic Criteria	Association with PCOS	Ethnicity	Conclusion
15155816	IRS-2 and IRS-4			Women with PCOS were identified based on a history of oligo/amenorrhoea, hirsutism, and typical morphological appearance of polycystic ovaries	Related	11 women with PCOS and 10 regularly cycling control women	This data demonstrates cell-specific alterations in IRS protein concentrations in theca cells from polycystic ovaries that are consistent with an exaggerated amplification of the insulin signal and which may play an important role in ovarian hyperandrogenism and thecal hyperplasia.
15705377	CYP21		G972R variant	�Inclusion criteria were evidence of ovulatory dysfunction in conjunction with hirsutism and/or hyperandrogenemia, as well as exclusion of other disorders, such as nonclassic 21-hydroxylase-deficient adrenal hyperplasia (NCAH), Cushing's syndrome, hyperpr	Related	PCOS (n = 114) and healthy controls (n = 95)	This IRS1 variant and CYP21 mutations seem to play a limited role in the development of PCOS
16037106	IRS-2			PCOS was defined by oligo-ovulation, clinical and/or biochemical hyperandrogenism and exclusion of hyperprolactinaemia (serum prolactin <24 g/l), non-classic congenital adrenal hyperplasia [adrenocorticotrophic hormone (ACTH)-stimulated 17-hydroxyprogest	Related	Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women	The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS.
16505239	ERK1/2 and MEK1/2			Women with PCOS had six or fewer menses per year and elevated total testosterone and/or nonsex hormonebinding globulinbound testosterone levels	Related	Women with PCOS (n = 20) and control (n=15)	ERK1/2 activation inhibits association of IRS-1 with p85 via IRS-1 Ser312 phosphorylation,
20229450			variant in gene		Related	65 women with PCOS and 27 age-matched healthy women	The IRS-1 Gly972Arg has the highest frequency reported world-wide for PCOS women. This variant is associated with insulin resistance and higher fasting insulin in PCOS women.
20210696	IRS-2				Related	183 women with PCOS and 88 healthy womens	IRS-1 polymorphism is associated with increased susceptibility to PCOS in a Greek population
20170352	C825T				Related	53 female patients with diagnosis of PCOS and 21 healthy women	The Gly972Arg and C825T polymorphisms are associated neither with PCOS nor with metabolic syndrome in the Slovak female population.
20012307					Related	162 women with PCOS and 122 regularly menstruating	IRS-1 gene should not be viewed as major contributor to the development of PCOS
18222120					Related	50 women with PCOS and 75 healthy women	The data do not support an association between G972R variant of the IRS-1 with PCOS or its metabolic parameters in Southern Chilean women.
17719609	ENPP1				Related	123 Japanese women with PCOS and 380 healthy Japanese controls	IRS-1 Gly972Arg polymorphism is associated with PCOS
17204522				Rotterdam criteria	Related	12 women with PCOS before, and 3 months after,laparoscopic ovarian electrocautery where analysed	Our results demonstrated that LOE effectively ameliorated insulin resistance in women with PCOS via decreased IRS-1 Ser(312) phosphorylation.
16603055				Rotterdam criteria	Related	47 Taiwanese Hoklo and Hakka women with PCOS and45 healthy	Not associated with the elevated risk of PCOS
16084882			G972A variant	The diagnosis of PCOS was based on the following criteria: sonographic polycystic ovary appearance, oligo/amenorrhea, and clinical (Ferriman-Gallwey score >8, acne persisting through the second decade of life, or androgenetic alopecia) or biochemical hype	Related	60 women with PCOS and 60 control women matched for age.	We observed that the G972A variant of IRS-1 was more prevalent in women with PCOS, and that it had important metabolic effects without having a direct effect on the androgen levels. However, the G972A variant of IRS-1 may modulate reproduction by lowering sex hormone-binding globulin in both healthy women and women with PCOS.
15840294	tyrosine phosphorylation				Related		IRS-1 tyrosine phosphorylation in adipose tissue in the two PCOS groups decreased markedly than in the non-obese control group
15130378	tyrosine phosphorylation	Insulin Resistant			Related	PCOS with insulin resistance (group A, n = 19), PCOS without insulin resistance (group B, n = 10) and controls group (n = 15)	IRS-1 in adipose tissue from polycystic ovary syndrome patients may be one of the mechanisms leading to insulin resistance.
12213887	IRS-2			NIH criteria	Related	227 PCOS subjects including 126 and 48 nondiabetic white and African-American	The results suggest that the IRS-2 Gly(1057)Asp polymorphism influences blood glucose levels in nondiabetic white and African-American women with PCOS. Thus, individuals with the common IRS-2 Gly/Gly genotype may be at increased risk of developing type 2 diabetes.
11522686	IRS-2		variant in Gly972Arg and Gly1057Asp	Diagnosis of PCOS was based on prolonged oligomenorrhea and/or amenorrhea and two of the following criteria:1) hyperandrogenism (androstenedione and/or testosterone),2) increased LH-to-FSH ratio (>2), and3) criteria for PCOS in a transvaginal ultrasoun	Related	HOMA(IR) n = 53and control subjects n = 102	The study concludes that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS.
11440917				The PCOS women had irregular menstrual cycles (6 menses per year) and an elevated total testosterone (T) and/or non-sex-hormone-binding globulin-bound testosterone (uT) level	Direct	PCOS (n = 14) compared with control (n = 12) muscle	The abundance of IRS-2 was significantly increased (P < 0.05) in PCOS skeletal muscle, suggesting a compensatory change. We conclude that there is a physiologically relevant defect in insulin receptor signaling in PCOS that is independent of obesity and type 2 diabetes mellitus.
10973656	IRS-2				Related	4 women with a histologic diagnosis of PCOS and 7 control	This study highlights a shift of the follicular insulin signal protein from IRS-1 to IRS-2 in insulin-resistant states and suggests an association between this change and ovarian abnormality in PCOS and gestational diabetes mellitus.
22205343	IRS-2			NIH criteria	Related	48 Iranian women diagnosed withPCOS and 52 non-diabetics, non-PCOS women	Considering that no association between the IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms and PCOS were found, the results confirm that these polymorphisms should not be considered as major contributors to the pathogenesis of this disorder.
22523112	IRS2		G972A		Direct	1,358 cases and 1,561 controls for Gly972Arg and 519 cases and 883 controls for Gly1057Asp	The meta-analysis suggested that IRS-1 Gly972Arg polymorphism might be considered a significant risk for PCOS.
22575725	PPAR-				Related	250 PCOS cases and 299 controls	Our study on Indian women suggests that while IRS-1, contrary to the earlier findings in other ethnic groups, seems to have a probable protective role against development of specific PCOS sub-phenotypes, the evidence for a probable protective role of PPAR is reaffirmed in our study.
22575725	PPAR				Direct	250 PCOS cases, 299 controls	This study on Indian women suggests that while IRS-1, contrary to the earlier findings in other ethnic groups, seems to have a probable protective role against development of specific PCOS sub-phenotypes