Association between INS-VNTR polymorphism and polycystic ovary syndrome in a Korean population

Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive ages. But its etiology is not fully understood yet. Variability in the number of tandem repeats of the insulin gene (INS-VNTR) is known to associate with PCOS, and it is associated with an increased risk of diabetes mellitus and other cardiovascular diseases. The aim of our study was to analyze an association between the INS-VNTR polymorphism and PCOS in a Korean population. The -23/Hph I polymorphism was used as a surrogate marker for INS-VNTR polymorphism and a total of 218 PCOS patient and 141 control DNAs were analyzed by restriction fragment length polymorphism method. Statistical analysis of genotyping results were performed using HapAnalyzer. χ(2) test and logistic regression were used to analyze the association between two groups. A p value <0.05 was considered statistically significant. The frequencies of A/A and A/T genotypes indicated a similar change between PCOS patients and controls. In conclusion, there was no association between PCOS and INS-VNTR polymorphism (p = 0.0544, odds ratio = 1.69). Our present data demonstrate that INS-VNTR polymorphism is not related with PCOS in Korean women. Thus, it is suggested that INS-VNTR polymorphism is not a key factor in the etiology and the pathogenesis of PCOS in a Korean population.     

Relationship between leptin receptor and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, which is involved in the multi-system disease, and its etiology is still not clearly understood. It is currently considered that not only the genetic factors but also the environment factors play a crucial role in the pathogenesis of PCOS. Obesity plays an important role through the insulin, leptin and endocannabinoid system in the pathological process of PCOS, leading to more severe clinical manifestations. The aim of our present study is to investigate whether there is association between single nucleotide polymorphisms (SNPs) of Gln223Arg and Pro1019Pro in the leptin receptor gene (LEPR) and PCOS in a Korean population. Interestingly, a significant association was found between the Pro1019Pro in LEPR gene and PCOS, and a highly significant association was found between the Gln223Arg in LEPR gene and PCOS (P = 0.033, OR = 1.523, 95% confidence interval and P < 0.0001, OR = 0.446, 95% confidence interval). Moreover, genotype combination and haplotype analyses indicate that Gln223Arg and Pro1019Pro polymorphisms of LEPR are significantly associated with the risk of PCOS.     

Association between vaspin rs2236242 gene polymorphism and polycystic ovary syndrome risk

Vaspin, an adipocytokine that has been isolated from the visceral adipose tissue, is a member of the serine protease inhibitor family. In humans, serum vaspin levels are correlated with body mass index (BMI) and obese women with polycystic ovary syndrome (PCOS). The present study is the first investigation to examine the association between vaspin rs2236242 gene polymorphism and risk of PCOS in Iranian patients. This case–control study was performed on 150 patients with PCOS and 150 healthy women. The vaspin genotypes were determined using tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Our finding showed that there are significant differences in genotype frequencies between case and control group regarding vaspin rs2236242 polymorphism (OR = 0.59, CI = 0.37–0.95, p = 0.03). The A allele decreased the risk of PCOS (OR = 0.67, CI = 0.46–0.96, p = 0.03) as compared to the T allele. There was no significant association between vaspin rs2236242 gene polymorphism and PCOS after adjusting genotypes for BMI. In conclusion, our data suggest a significant association between vaspin rs2236242 polymorphism and the PCOS but this relationship is affected by obesity status.     

Association between polymorphisms of the CYP11A1 gene and polycystic ovary syndrome in Chinese women

The cholesterol side chain cleavage enzyme (CYP11A1) gene plays an important part in the synthesis of sex hormones and has been reported to be involved in the pathogenesis of polycystic ovary syndrome. A case-control study including 314 PCOS patients and 314 controls was conducted to assess the association of the SNPs rs4077582 and rs11632698 in CYP11A1 with PCOS using the polymerase chain reaction-restriction fragment length polymorphism method. Thereafter, 100 DNA samples were re-genotyped by direct sequencing for confirmation. The genotypic distribution of rs4077582 in women with PCOS differed from that in controls (P = 0.002). No such distributional difference was found in rs11632698 (P = 0.912). Data from our previous study of these two SNPs in another population including 290 PCOS patients and 344 controls was combined with the current data. Combined analysis (a total of 1262 participants, including 604 PCOS patients and 658 control women) showed a much more significant difference in the genotypic distribution of rs4077582 between PCOS and controls (P < 0.001). The T allele was more prevalent in PCOS patients (Odds ratio = 1.314; 95 % CI 1.122-1.540). The testosterone levels among the three genotypes for rs4077582 were different in the control group, as were the LH levels and the LH/FSH ratio. Therefore, SNP rs4077582 in CYP11A1 is strongly associated with susceptibility to PCOS and may alter the testosterone levels by the regulation of LH in different genotypes. No association was observed in rs11632698.     

Metabolic syndrome in polycystic ovary syndrome

Both metabolic syndrome (MS) and polycystic ovary syndrome (PCOS) are common among women. The exact prevalence of MS in women with PCOS is dependent upon the diagnostic criteria used for each. However, the frequent co-occurrence of both MS and PCOS in women is suggestive of a common aetiology. In this short review article we argue that insulin resistance, as a consequence of abdominal obesity, may represent such a common aetiology. We also review the literature on the prevalence of MS in women with PCOS and consider the impact that the particular criteria used to diagnose both MS and PCOS may have had on these estimates of prevalence.     

Association between copy-number variation on metabolic phenotypes and HDL-C levels in patients with polycystic ovary syndrome

Polygenic diseases with a broad phenotypic spectrum, such as polycystic ovary syndrome (PCOS), present a particular challenge in terms of identifying the underlying genetic mechanisms, nevertheless genetic variants have impact on the individual phenotype. We aimed to determine if next to genetic variations like SNPs further mechanisms might play a role in the pathogenesis of PCOS. We examined the effect of copy-number variations (CNVs) on metabolic phenotypes in PCOS. The intragenic rs1244979, rs2815752 in NEGR1 gene, and rs780094 in GCKR gene were genotyped and CNVs were determined by droplet digital polymerase chain reaction (ddPCR) in PCOS patients (n?=?153) and controls without metabolic syndrome (n?=?142). The study indicated that SNPs are not associated with the pathogenesis of PCOS but affect metabolic phenotypes. The CNVs investigated show a lower variability in PCOS than in CON. Furthermore, we provided direct evidence that the copy number, but not the genotype of the CNV in the genomic regions of rs780094(GCKR) is associated with low level of high-density lipoprotein cholesterol in PCOS. This study supports the hypothesis that not only genetic variants, but also CNVs in metabolically relevant genes, have an effect on metabolic phenotypes in our group of PCOS patients.     

Proteomics and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder of heterogeneous etiology. Proteomics techniques have been used for elucidating the physiopathology of PCOS, yet the proteins identified so far were rarely the same across tissues and studies. The present review discusses the current challenges in the application of proteomics to the study of PCOS. A well-defined research design and an appropriate selection of study populations, samples and proteomic platforms are essential in clinical proteomics. Furthermore, the findings derived from proteomic approaches should be validated by complementary techniques, and the reproducibility of the results has ideally to be confirmed by different studies. Only when meeting these requirements, the proteins identified by proteomic techniques should be considered as candidates for future studies aiming to define specific molecular phenotypes of PCOS and their possible role in the metabolic and hormonal abnormalities characteristic of this syndrome.     

Neuroendocrine dysfunction in polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is a common disorder characterized by ovulatory dysfunction and hyperandrogenemia (HA). Neuroendocrine abnormalities including increased gonadotropin-releasing hormone (GnRH) pulse frequency, increased luteinizing hormone (LH) pulsatility, and relatively decreased follicle stimulating hormone contribute to its pathogenesis. HA reduces inhibition of GnRH pulse frequency by progesterone, causing rapid LH pulse secretion and increasing ovarian androgen production. The origins of persistently rapid GnRH secretion are unknown but appear to evolve during puberty. Obese girls are at risk for HA and develop increased LH pulse frequency with elevated mean LH by late puberty. However, even early pubertal girls with HA have increased LH pulsatility and enhanced daytime LH pulse secretion, indicating the abnormalities may begin early in puberty. Decreasing sensitivity to progesterone may regulate normal maturation of LH secretion, potentially related to normally increasing levels of testosterone during puberty. This change in sensitivity may become exaggerated in girls with HA. Many girls with HA-especially those with hyperinsulinemia-do not exhibit normal LH pulse sensitivity to progesterone inhibition. Thus, HA may adversely affect LH pulse regulation during pubertal maturation leading to persistent HA and the development of PCOS.     

The prevalence of polycystic ovary syndrome in a community sample of Iranian population: Iranian PCOS prevalence study

Background  

Despite the heavy burden and impact of the polycystic ovary syndrome (PCOS) in reproduction and public health, estimates regarding its prevalence at community levels are limited. We aimed to ascertain prevalence of PCOS in a community based sample using the National Institute of Health (NIH), the Rotterdam consensus (Rott.) and the Androgen Excess Society (AES) criteria.     

Age associated differences in prevalence of individual rotterdam criteria and metabolic risk factors during reproductive age in 446 caucasian women with polycystic ovary syndrome

Clinical manifestations and metabolic risk factors may differ according to age in patients with polycystic ovary syndrome (PCOS). Therefore, a retrospective trans-sectional study in academic tertiary-care medical center was designed. A cohort of 446 premenopausal, Caucasian women (age range 15-49 years) with PCOS were divided into 4 subgroups according to age: group 1 (15-19 years, n=42), group 2 (20-29 years, n=180), group 3 (30-39 years, n=187), group 4 (40-49 years, n=37) and underwent clinical evaluation (Ferriman-Gallwey score, BMI, waist, blood pressure), hormone analyses (sex hormones, fasting lipids, insulin, glucose), transvaginal ultrasound, oral glucose tolerance tests (OGTT) (n=234), and ACTH tests (n=201). BMI, waist, Ferriman-Gallwey score, blood pressure, and lipid profile were higher in older vs. younger age groups whereas androgen levels were lower. Measures of insulin resistance were unchanged between age groups, but glucose levels were significantly higher in older age groups. Rotterdam criteria: The prevalence of PCO and biochemical hyperandrogenism decreased in the oldest age group whereas clinical hyperandrogenism increased. Young patients are characterized by PCO and biochemical hyperandrogenism, whereas older patients are more obese with more severe hirsutism and more cardiovascular and metabolic risk factors.     

多囊卵巢综合征患者与健康人群肠道菌群差异性分析

目的 比较多囊卵巢综合征(PCOS)患者与健康人群间肠道菌群的差异,为后续研究提供参考.方法 采用16SrDNA扩增子测序法对30例PCOS患者(PCOS组)和20例健康人(健康组)粪便标本中菌群结构进行分析,并比较两组之间的区别.结果 与健康组相比,PCOS组患者肠道菌群α多样性降低.PCOS组患者肠道厚壁菌门(Fi...     

Inappropriate gonadotropin secretion in the polycystic ovary syndrome

In this study was investigated the diagnostic significance of double stimulation test with (that is of 25 micrograms rapid injection intravenously twice at an interval of 120 minutes and the misure of maximal net increment of serum LH after the first GnRH injection expressed as delta 1 and after the second injection, expressed as delta 2) to discriminate patients with idiopatic hirsutism. This test was effectuated on 8 patients with PCO (presence of polycystic ovaries on Ecografya and/or Laparoscopy) and 8 patients with idiopatic hirsutism (presence of normal morphology ovaries). Basal LH, FSH, E1, E2 and delta 4 levels were also measured. The value of LH delta 2 were more elevated in patients with PCO (p less than 0,0002) than the patients with idiopatic hirsutism. Consequently it as been value of LH delta 2 to discriminate the two different groups of patients. In PCO patients were also found: -a positive linear correlation between LH delta 1 and basal concentration serum of E2 (p less than 0,001); -a significant increase of basal levels serum of delta 4 (p less than 0,02); while the values of basal LH and LH delta 1 were found superior only on 4 of the initial 8 patients, the basal values of E1 and E2 were at the superior found of the norm and basal FSH, FSH delta 1 and FSH delta 2 values were found normals.     

Genetic aspects of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amenorrhoea (or oligomenorrhoea), hyperandrogenism, hirsutism, obesity, insulin resistance, and an approximately 7-fold increased risk of type 2 diabetes mellitus (NIDDM - non-insulin dependent diabetes mellitus). It is a leading cause of female infertility. The prevalence of PCOS among reproductive-age women has been estimated at 4%-12%. Familial aggregation of this syndrome is well established. There are also ethnic and racial variations in the prevalence of the syndrome and its symptoms. Multiple biochemical pathways have been implicated in the pathogenesis of PCOS. Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1, ACTR2A-B, FS, INHA, INHBA-B, INHC, SHBG, LHCGR, FSHR, MADH4, AR), obesity and energy regulation (MC4R, OB, OBR, POMC, UCP2-3), insulin secretion and action (IGF1, IGF1R, IGFBPI1-3, INS VNTR, IR, INSL, IRS1-2, PPARG) and many others. Most women with PCOS, both obese and lean, have a degree of insulin resistance. The minisatellite of insulin gene (INS VNTR), especially class III alleles and III/III genotypes might not only determine the predisposition to anovulatory PCOS but also the concomitant risk for development of type 2 diabetes. The function of the insulin receptor (IR) is probably normal in woman with PCOS. However abnormal serine phosphorylation in the receptor may impair signal transduction accounting for a post-binding defect in insulin action. Serine phosphorylation is also involved in the postranslational regulation of 17,20-lyase activity (CYP17). There may be a common aetiology for both insulin resistance and hyperandrogenism. Polymorphic alleles of both IRS-1 and IRS-2 (insulin receptor substrate 1 - 2), alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. There is no evidence to suggest that follistatin gene polymorphisms play a role in the pathogenesis of insulin resistance in PCOS women. PCOS appears to be associated with the absence of the four-repeat-units allele in a polymorphic region of pentanucleotide (TTTTA)n repeats within CYP11A gene, which encodes cytochrome P450scc. It has been hypothesized that up-regulation of this enzyme could lead to increased androgen production. There is no evidence of any association of alleles of CYP19 gene (encoding cytochrome P450arom) with PCOS. Association exists between androgen receptor gene (AR) polymorphisms an androgens action in PCOS. Increased hirustism and decreased CAG repeat length within AR gene has been also demonstrated in women with normal testosterone levels. Expression of estrogen receptor (ERs) as well as 5-alpha-reeducates (SRD5A1-2 genes) activity was analysed in granulosa (GC) and theca cells (TC). The results of this study demonstrate that there are significant alterations in the expression of ERalpha and ERbeta in PCOS that may be related to abnormal follicular development. On the other hand elevated SRD5A activity in polycystic ovaries supported the hypothesis that 5-alpha-reduced androgens may play a role in the pathogenesis of the syndrome. The genetic aetiology of PCOS remains unknown. There are a number of interlinking factors that affects expression of PCOS. Single cause of PCOS is unlikely. Other possible mechanisms in pathogenesis of PCOS are discussed.     

Modelling the control of ovulation and polycystic ovary syndrome

 The control of ovulation in mammalian species appears to be a highly robust process. The primary mechanism is believed to be competition amongst a group of developing follicles, mediated by a hormonal feedback loop involving in the first instance the pituitary. Successful follicles reach maturity and ovulate, the remainder atrophy and die. A model of this control process has been derived by Lacker and his group. Based on simple qualitative assumptions about the hormonal feedback loop, this is able to reflect many of the basic physiological features of ovulation in mammals. However, a fundamental hypothesis of Lacker’s work is that all follicles are identical and respond to hormonal signals in precisely the same way. Not only is this improbable, but it also leads to several aspects of the model which are qualitatively unrealistic, most notable of these is its inability to accurately model the condition known as Polycystic Ovary Syndrome. This common malfunction of the ovulatory control mechanism accounts for up to three-quarters of cases of anovulatory infertility in humans and its understanding is therefore of considerable medical significance. In this paper we extend the analysis of Lacker’s model to the case of non-identical follicles; this allows us to obtain behaviour much closer to that observed in PCOS patients and to draw some tentative conclusions about the mechanisms underlying this condition. Received 19 August 1996; received in revised form 14 February 1997     

Intravenous glucose tolerance test in the polycystic ovary syndrome

The problem of hyperinsulinism and insulin resistance, previously observed by us in PCOS using the tolbutamide test, was studied in the present research using intravenous glucose tolerance test (IVGTT). 16 women (3 obese) aged 14-34 years, affected by PCOS, were studied. The diagnosis of PCOS was made using clinical, hormonal, radiologic and echographic criteria. 8 age matched healthy women were used as controls. Glucose and insulin curves, glucose (GA) and insulin (IA) response areas and IA/GA ratio (insulin resistance index-IRI-) were studied by IVGTT. Both the mean insulin peak and the mean insulin area were significantly more elevated in patients than in controls. Average IRI value also was significantly higher than that of controls. The presence of both an hyperinsulinism and an insulin resistance is shown by the higher values in patients compared to controls. No correlation was found between either insulin areas or IRI values with plasma testosterone and urinary dehydroisoandrosterone, whereas correlations were demonstrated in previous studies, using OGTT, by us and other Authors and by us using tolbutamide test. The difference in the nature of the various stimuli performed seems to explain the different results.     

Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women

Background  

Tribbles 3 (TRB3) affects insulin signalling by inhibiting insulin-stimulated Akt phosphorylation and subsequent activation. A single nucleotide polymorphism located in the second extron of the human TRB3 gene is thought to be associated with insulin resistance. The latter is a core abnormality in PCOS independent of obesity. The present study was designed to clarify the relationships of TRB3 Q84R polymorphism with PCOS in a Chinese women group.