Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population

Baba, Tsuyoshi; Endo, Toshiaki; Sata, Fumihiro; Honnma, Hiroyuki; Kitajima, Yoshimitsu; Hayashi, Takuhiro; Manase, Kengo; Kanaya, Mika; Yamada, Hideto; Minakami, Hisanori; Kishi, Reiko; Saito, Tsuyoshi

doi:10.1016/j.lfs.2007.07.023

Cited by 39 publications

(37 citation statements)

References 34 publications

(32 reference statements)

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“…After review, a total of 16 published articles reported on the relationship between these two IRS gene polymorphisms and PCOS met the inclusion criteria [12][13][14][15][19][20][21][22][23][24][25][26][27][28][29], 15/16 were about the Gly972Arg polymorphism, 5/16 were about the Gly1057Asp polymorphism. These articles were published between 2001 and 2011.…”

Section: Eligibility Of Studiesmentioning

confidence: 99%

Association of IRS-1 and IRS-2 genes polymorphisms with polycystic ovary syndrome: a meta-analysis

Ruan

Xie

2012

Endocr J

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POLYCYSTIC OvarY SYndrOme (PCOS)is one of the most common heterogeneous endocrine disorders, which affect 5%-10% of women in reproductive age and is a leading causes of female infertility [1]. It is characterized by menstrual irregularity, hyperandrogenism, insulin resistance, and increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [2,3]. Candidate genes for etiology of PCOS involve in ovarian and adrenal steroidogenesis, steroid hormone actions, gonadotropin action and regulation, insulin action and secretion, energy homeostasis, chronic inflammation and others [4]. Yet the "PCOS genes" remain elusive. Insulin resistance is a key component in the pathogenesis of PCOS and the predisposition to type 2 diabetes [5,6], however, the mechanisms for defects in insulin signaling in the disorder are comAssociation of IRS-1 and IRS-2 genes polymorphisms with polycystic ovary syndrome: a meta-analysis Yuan Ruan, Jianhua Ma and Xiaojing Xie Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China abstract. Insulin resistance (IR) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS) which is a common disorder in premenopausal women. The association between the single nucleotide polymorphisms (SNPs) of insulin receptor substrate (IRS) gene and PCOS in several populations has been studied, but the results are conflicting. The aim of this study was undertaken to investigate association of IRS-1 and IRS-2 genes polymorphisms with PCOS by conducting a meta-analysis. Literature search was conducted through PubMed and EMBASE databases (up to July 31, 2011). Fifteen articles with 1,358 cases and 1,561 controls were enrolled in the meta-analysis of the association between Gly972Arg variant and PCOS, and five articles with 519 cases and 883 controls were enrolled in the meta-analysis of Gly1057Asp variant. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed and random-effects models. The Q-statistic test was used to assess heterogeneity, and Begg's test and Egger's test were used to evaluate publication bias. Sensitivity analysis was also performed. Our results indicated that A allele of Gly972Arg conferred a significantly increased risk of PCOS compared with G allele (OR = 1.91, 95% CI: 1.36-2.68). However, in Gly1057Asp polymorphism the OR of allele A vs. G is 0.92 (95% CI: 0.72, 1.18). Our meta-analysis suggested that IRS-1 Gly972Arg polymorphism might be considered a significant risk for PCOS. Otherwise, no significant associations were observed in IRS-2 Gly1057Asp polymorphism which needs to be further confirmed by further studies.Key words: Insulin receptor substrate, Polymorphisms, Polycystic ovary syndrome, Meta-analysis plex and have not been fully elucidated [7,8].Insulin receptor substrates proteins (IRS) are critical for insulin mediated signal transduction in insulin target tissues. Several studies have shown that two common polymorphisms in IRS particularly Gly972Arg (rs1801278) in ...

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Section: Eligibility Of Studiesmentioning

confidence: 99%

Association of IRS-1 and IRS-2 genes polymorphisms with polycystic ovary syndrome: a meta-analysis

Ruan

Xie

2012

Endocr J

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“…The allele and genotype frequencies of IRS-2 Gly1057Asp and IRS-1 Gly972Arg of the control come from the study of Chan 16 and Baba. 17 Genotype distribution of IRS-2 Gly1057Asp and IRS-1 Gly972Arg SNPs matched with the Hardy-Weinberg equilibrium (p40.05). Furthermore, there were no significant differences in the distribution of genotypes between the two groups (p50.05) ( Table 6).…”

Section: Genotyping Analysis and Allelic Frequenciesmentioning

confidence: 86%

Tacrolimus decreases insulin sensitivity without reducing fasting insulin concentration: a 2-year follow-up study in kidney transplant recipients

Chen

Zuo

et al. 2015

Renal Failure

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New Onset Diabetes after Transplantation (NODAT) is defined as sustained hyperglycemia developing in patients without diabetes history before transplantation. A cohort study was performed to access the effects of tacrolimus on insulin secretion and insulin sensitivity and consequently in the development of NODAT in kidney transplant recipients. Then, we further investigated the association between NODAT and single-nucleotide polymorphisms of IRS-1 and IRS-2 in renal allograft recipients. One hundred and fifty-eight kidney transplant patients, receiving tacrolimus as the base immunosuppressant, were divided into two groups: with or without NODAT. Plasma levels of fasting insulin concentration (FINS) and C-peptide were determined by enhanced chemiluminescence immunoassay and ADVIA Centaur C peptide assay, respectively. The genotypes of Gly1057Asp in IRS-2 and Gly972Arg in IRS-1 were detected through polymerase chain reaction fragment length polymorphism in NODAT and non-NODAT patients. It was found that the concentrations of fasting plasma insulin and C-peptide in NODAT and non-NODAT patients treated with tacrolimus were higher than that in healthy volunteers (p50.05). Fasting plasma insulin concentration in NODAT was significantly elevated compared with than that in non-NODAT group (p50.05). But there are no statistical differences in fasting plasma C-peptide concentrations between NODAT and non-NODAT groups. The allele and genotype frequencies of IRS-2 Gly1057Asp and IRS-1 Gly972Arg in NODAT patients were not significantly different from non-NODAT patients (p40.05). In conclusion, insulin resistance is the primary cause of tacrolimus-induced NODAT. The IRS-2 Gly1057Asp and IRS-1 Gly972Arg genotypes are not related to NODAT.

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“…Gly972Arg polymorphism of IRS-1 reduces its phosphorylation and allows IRS-1 to act as an inhibitor of the INSR kinase, thereby impairing insulin signaling [41]. This polymorphism has shown significant association with PCOS in Italian [42], Greek [43], Japanese [44], and Turkish [45] [53,54]. A Mendelian meta-analysis has confirmed significant association of IRS-1 (Gly972Arg) polymorphism with the risk of developing PCOS and impaired insulin signaling [36].…”

Section: Irsmentioning

confidence: 94%

“…A study in Finnish women strongly implicates the role of this polymorphism in PCOS susceptibility [58]. However subsequent studies in Spanish [59], Japanese [44], and Saudi [60] women demonstrated no association with PCOS and its related metabolic or hormonal traits.…”

Section: Enpp1mentioning

confidence: 99%

Genetic Markers of Polycystic Ovary Syndrome: Emphasis on Insulin Resistance

Shaikh

Dadachanji

Mukherjee

2014

International Journal of Medical Genetics

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Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of childbearing age causing not only reproductive but also metabolic anomalies. PCOS women present with ovulatory dysfunction, abnormal hormones, hyperandrogenemia, obesity, and hyperinsulinemia. It is a heterogeneous disorder which results from interaction of multiple genes along with environmental factors. Insulin resistance is a central key element contributing to PCOS pathogenesis and is further aggravated by obesity. Insulin regulates metabolic homeostasis and contributes to ovarian steroidogenesis. Candidate gene analyses have dissected genes related to insulin secretion and action for their association with PCOS susceptibility. Although a large number of genomic variants have been shown to be associated with PCOS, no single candidate gene has emerged as a convincing biomarker thus far. This may be attributed to large amount of heterogeneity observed in this disorder. This review presents an overview of the polymorphisms in genes related to insulin signaling and their association with PCOS and its related traits.

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Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population

Cited by 39 publications

References 34 publications

Association of IRS-1 and IRS-2 genes polymorphisms with polycystic ovary syndrome: a meta-analysis

Association of IRS-1 and IRS-2 genes polymorphisms with polycystic ovary syndrome: a meta-analysis

Tacrolimus decreases insulin sensitivity without reducing fasting insulin concentration: a 2-year follow-up study in kidney transplant recipients

Genetic Markers of Polycystic Ovary Syndrome: Emphasis on Insulin Resistance

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