An insight of association of insulin resistance with polycystic ovary syndrome (original) (raw)
Related papers
Genetic Markers of Polycystic Ovary Syndrome: Emphasis on Insulin Resistance
International Journal of Medical Genetics, 2014
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.
Divergences in Insulin Resistance Between the Different Phenotypes of the Polycystic Ovary Syndrome
The Journal of Clinical Endocrinology & Metabolism, 2013
Context/Objective: Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women.
Molecular Study of Insulin Resistance and Polycystic Ovary Syndrome
American Journal of Medicine and Medical Sciences, 2015
This study explores on the relationship between the polycystic ovary syndrome (PCOS) and insulin resistance which caused by variation in the 5-prime flanking region of the insulin gene, a which regulates transcription of the gene. The study includes 50 Iraqi women with polycystic ovary syndrome (PCOS) and 50 healthy women, Blood samples were collected from the Medical City hospital, Kamal al-Samarrai Hospital and private medical laboratories (in Baghdad), during the period from November, 2011 to May, 2012. The age of infertile and fertile women was ranged from 16 to 45 years. The molecular study was focused on the 42% of PCOS women with insulin resistance. By sequencing for 50 samples, one separate segment (promoter) containing nucleotide 360 of insulin gene was amplified by using specific primer. The result of sequencing refers to a number of mutations found in women with PCOS (substitution = 69.86%, deletion =10.95% and insertion =19.17%). Also compound mutations have been detected among most of PCOS with insulin resistance.
Archives of Gynecology and Obstetrics, 2010
Purpose The aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance. Methods The study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR–restriction fragment length polymorphism (RLFP) assay. Results No association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected. Conclusion The G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.
Fertility and Sterility, 2011
Objective-To evaluate association with polycystic ovary syndrome (PCOS) of 295 variants in 39 genes central to metabolic insulin signaling and glycogen synthase kinase-3β (GSK-3β) regulation, followed by replication efforts. Design-Case-control association study, with discovery and replication cohorts. Setting-Subjects were recruited from reproductive endocrinology clinics, controls were recruited from communities surrounding the University of Alabama at Birmingham and Erasmus Medical Center. Patients-273 cases with PCOS and 173 controls in the discovery cohort; 526 cases and 3585 controls in the replication cohort. All subjects were Caucasian. Interventions-Phenotypic and genotypic assessment. Main Outcome Measures-295 SNPs, PCOS status. Results-Several SNPs were associated with PCOS in the discovery cohort. Four insulin receptor (INSR) SNPs and three insulin receptor substrate 2 (IRS2) SNPs associated with PCOS
Fertility and Sterility, 2010
To assess the role of the insulin receptor gene in polycystic ovary syndrome (PCOS) we performed a case-control study in a female population (n ¼ 226) from Central Europe by examining the genetic associations of single nucleotide polymorphisms (rs8107575, rs2245648, rs2245649, rs2963, rs2245655, and rs2962) and inferred haplotypes around exon 9 of this gene. The ancestral T allele of single nucleotide polymorphism rs2963 or the corresponding haplotype (GGTC-C) showed association with PCOS with odds ratio 2.99, 95% confidence interval 1.4-6.3, independent of obesity but related to the presence of Acanthosis nigricans and insulin resistance, metabolic syndrome, or hyperandrogeny, thus providing a frame for future fine mapping of the susceptibility loci in PCOS. (Fertil Steril Ò 2010;94:2389-92.
Molecular & genetic factors contributing to insulin resistance in polycystic ovary syndrome
2010
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of unknown etiology. Insulin resistance is very common and plays a central pathogenic role in PCOS. During last decade several studies have been conducted to understand the mechanisms contributing to the state of insulin resistance and insulin-induced hyperandrogenemia in PCOS. Insulin signaling pathways have been dissected in different insulin responsive tissues such as skeletal muscles, adipose tissues, fibroblasts as well as ovaries to elucidate the mechanism. These studies suggest a post receptor signaling defect where metabolic action of insulin is affected but not the steroidogenic and mitogenic actions. Despite advancement in these studies gaps exist in our understanding of the mechanism of insulin resistance as well as insulininduced steroidogenesis in PCOS. The syndrome is now considered as a complex multigenic disorder. Efforts are ongoing to dissect the variants of genes from multiple logical pathways which are involved in pathophysiology of the syndrome. But still today no gene has been emerged as universally accepted susceptibility gene for PCOS. This review briefly describes the lacunae along with the current status of molecular events underlying insulin resistance and the contribution of insulin signaling pathway genes in pathogenesis of PCOS along with future researchable areas.
2006
Background: Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS) are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, especially Gly972Arg/ Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. We intended to assess the prevalence of abnormal glucose tolerance (AGT) and insulin resistance in Taiwanese PCOS women. We also tried to assess whether the particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene mutation can be used as an appropriate diagnostic indicator for PCOS. Methods: We designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka women, diagnosed with PCOS were enrolled in this study as were forty-five healthy Hoklo and Hakka women as the control group. Insulin resistance was evaluated with fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment index for insulin resistance (HOMA IR). The genomic DNA of the subjects was amplified by PCR and digested by restriction fragmented length polymorphism (RFLP) with Bst N1 used for codon 972 and Dra III for codon 513. Results: AGT was found in 46.8% of these PCOS patients and was significantly related to high insulin resistance rather than the low insulin resistance. Those patients with either insulin resistance or AGT comprised the majority of PCOS affected patients (AGT + fasting insulin 17: 83%, AGT + glucose/insulin ratio 6.5: 85.1%, AGT + HOMA IR 2: 87.2%, and AGT + HOMA IR 3.8: 72.3%). None of the tested samples revealed any polymorphism due to the absence of any Dra III recognition site or any Bst N1 recognition site in the amplified PCR fragment digested by restriction fragmented length polymorphism. Conclusion: There is significantly high prevalence of AGT and insulin resistance in PCOS women, but Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not associated with the elevated risk of PCOS amongst Taiwanese subjects. This is quite different from the similar study in phylogenetically diverged Caucasian subjects.
2007
BACKGROUND: Polycystic ovary syndrome (PCOS) is non-uniformly associated with insulin resistance (IR). We examined IR in women with PCOS. METHODS: Sixty-nine PCOS women were subjected to the insulin suppression test (IST) to determine their steady-state plasma glucose (SSPG) as a direct measure of insulin sensitivity. RESULTS: SSPG exhibited a multimodal distribution suggesting the existence of subpopulations. The heterogeneous distribution of plasma glucose at 180 min (P 5 0.011), with three modes, suggested differences in the plasma glucose level trajectories during the IST. Hence, the population was separated into three groups: (i) (n 5 33), subjects with SSPG 152.5 mg/dl, corresponding to the first to fifth deciles; (ii) (n 5 29), subjects in the interval 152.5 mg/dl < SSPG 300 mg/dl; (iii) (n 5 7), subjects with SSPG > 300 mg/dl, corresponding to the tenth decile. Plasma glucose distributions at 180 min showed differences in their mean values and ranges among groups (P < 0.0001). The trajectories of the groups differed significantly during the IST (P < 0.0001). CONCLUSIONS: insulin sensitivity in our patients exhibited a discontinuous distribution, implying that PCOS is a heterogeneous disorder possessing subpopulations regarding IR.