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CYP1A1 gene (6235T<C) polymorphism as a risk factor for polycystic ovarian syndrome among Egyptian women.

CYP1A1 基因 (6235T<C) 多态性是埃及女性多囊卵巢综合征的危险因素。

  • 影响因子:1.34
  • DOI:10.1080/14647273.2018.1522455
  • 作者列表:"Bayoumy N","El-Shabrawi M","Younes S","Atwa K
  • 发表时间:2020-06-01
Abstract

:This case-control study was carried out to examine the association between CYP1A1 gene (6235T<C) polymorphism among Egyptian women with polycystic ovarian syndrome (PCOS). One hundred and twenty women with PCOS, as well as 120 apparently healthy women as controls, were included in this study. Blood samples were collected on the second or third day of the menstrual cycle for laboratory work-up. CYP1A1 gene (6235T<C) polymorphism was determined using restriction enzyme fragment length polymorphism - polymerase chain reaction (RFLP-PCR) technique. Women who carried the TC and CC genotypes showed insignificant increase in risk (1.4 and 2.7, respectively) for developing PCOS (p = 0.331 and p = 0.124, respectively). The risk showed a significant association among PCOS women with ovarian sonographic stigmata of polycystic ovaries (PCO) who carried the TC genotype (Odds Ratio (OR) = 1.92, p = 0.032), as well as among carriers of the CC genotype (OR = 4.2, p = 0.048). Both TC and CC genotypes were significantly associated with the ovarian volume (p < 0.001) and abdominal obesity (p = 0.025), while no associations were shown with the hormonal profile. In conclusion, both TC and CC genotypes of the CYP1A1 gene showed increased susceptibility to PCOS. CYP1A1 gene polymorphism may affect the folliculogenesis and the hormonal status along with other risk factors leading to the development of the full picture of PCOS.

摘要

: 本病例对照研究旨在检测埃及多囊卵巢综合征 (PCOS) 妇女 CYP1A1 基因 (6235T<C) 多态性之间的相关性。120 例 PCOS 妇女,以及 120 例明显健康的妇女作为对照,被纳入本研究。在月经周期的第二天或第三天采集血液样本进行实验室检查。采用限制性内切酶片段长度多态性-聚合酶链反应 (RFLP-PCR) 技术测定 CYP1A1 基因 (6235T<C) 多态性。携带 TC 和 CC 基因型的女性发生 PCOS 的风险无显著增加 (分别为 1.4 和 2.7) (分别为 p = 0.331 和 p = 0.124)。在卵巢超声检查多囊卵巢 (PCO) 携带 TC 基因型的 PCOS 妇女中,该风险显示出显著的相关性 (比值比 (OR) = 1.92,P = 0.032),以及 CC 基因型携带者 (or = 4.2,p = 0.048)。TC 和 CC 基因型均与卵巢体积 (p <0.001) 和腹型肥胖 (p = 0.025) 显著相关,而与激素谱无相关性。总之,CYP1A1 基因的 TC 和 CC 基因型均显示对 PCOS 的易感性增加。CYP1A1 基因多态性可能影响卵泡发生和激素状态以及导致 PCOS 全貌发展的其他危险因素。

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发表时间:2020-01-15
DOI:10.1016/j.mce.2019.110611
作者列表:["Makrinou E","Drong AW","Christopoulos G","Lerner A","Chapa-Chorda I","Karaderi T","Lavery S","Hardy K","Lindgren CM","Franks S"]

METHODS:Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age, whose aetiology remains unclear. To improve our understanding of the molecular mechanisms underlying the disease, we conducted a genome-wide DNA methylation profiling in granulosa lutein cells collected from 16 women suffering from PCOS, in comparison to 16 healthy controls. Samples were collected by follicular aspiration during routine egg collection for IVF treatment. Study groups were matched for age and BMI, did not suffer from other disease and were not taking confounding medication. Comparing women with polycystic versus normal ovarian morphology, after correcting for multiple comparisons, we identified 106 differentially methylated CpG sites with p-values <5.8 × 10 that were associated with 88 genes, several of which are known to relate either to PCOS or to ovarian function. Replication and validation of the experiment was done using pyrosequencing to analyse six of the identified differentially methylated sites. Pathway analysis indicated potential disruption in canonical pathways and gene networks that are, amongst other, associated with cancer, cardiogenesis, Hedgehog signalling and immune response. In conclusion, these novel findings indicate that women with PCOS display epigenetic changes in ovarian granulosa cells that may be associated with the heterogeneity of the disorder.

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影响因子:2.68
发表时间:2020-02-01
DOI:10.1080/14656566.2019.1701655
作者列表:["Vatopoulou A","Tziomalos K"]

METHODS::Introduction: Approximately 1% of adolescents have polycystic ovary syndrome (PCOS) and almost 40-70% of these patients are overweight or obese. Obese adolescents with PCOS have more severe insulin resistance and hyperandrogenemia, a more adverse lipid profile and a worse quality of life than normal-weight adolescents with PCOS. Accordingly, weight loss is an important component of the management of these patients.Areas covered: The authors discuss the different options for weight loss in obese adolescents with PCOS. Lifestyle changes appear to be effective but adherence to this intervention is suboptimal. There are also limited data regarding the optimal diet in this population. Few small studies have evaluated the effects of pharmacotherapy in these patients. Conflicting data have been reported regarding the effects of metformin on body weight. Notably, agents that have been approved for weight loss in adults have not been evaluated in adolescents with PCOS.Expert opinion: More studies are needed to identify the most appropriate diet for obese adolescents with PCOS. Well-designed randomized controlled studies are also needed to define the safety and efficacy of pharmacotherapy in this population.

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影响因子:2.78
发表时间:2020-02-01
DOI:10.1007/s11010-019-03678-6
作者列表:["Ding Y","He P","Li Z"]

METHODS::Polycystic ovary syndrome (PCOS) is a hormonal disorder common among women of reproductive age. Although much is understood concerning the pathology of PCOS, further investigation into the influence of microribonucleic acids (miRNAs) on the proliferation of ovarian granulosa cells (GCs) is needed. This study investigated the role of specific miRNAs in ovarian dysfunction of PCOS and its effect on the proliferation of GCs. Initially, miRNA profiling was performed on the ovarian cortexes of 15 rats in which PCOS had been induced and 15 rats without PCOS (non-PCOS). This mechanical study was performed on ovarian GCs extracted from human chorionic gonadotrophin (hCG)-induced rats. Insulin was used to treat GCs to establish the PCOS cell model. Increased Equus caballus mir-9119 expression was observed and confirmed in the insulin-induced model of PCOS in GCs (GC-PCOS) as well as in the hCG-induced rats when compared to non-PCOS rats and cells. Observation and confirmation were carried out through both miRNA array and quantitative PCR. In contrast, downregulation of the nuclear factor kappa B (NFκB) p65 was observed in the PCOS cell model. Additionally, annexin V, FITC, and propidium iodide flow cytometry showed overexpression of miR-9119-induced apoptosis. In this study, we revealed that miR-9119 inhibition regulates p65 expression levels in insulin-treated GCs by binding to the 3'-untranslated of p65. Additionally, regulation of p65 expression was positively correlated with the expression of the double-stranded RNA endoribonuclease DICER. Moreover, RNA silencing/overexpression of p65 affected the functional role of miR-9119. In conclusion, GCs of PCOS, the expression of miR-9119, and targeted NFκB/p65-DICER axis are upregulated in order to maintain cell viability and prevent apoptosis, thereby promoting Anti-Müllerian hormone production in GCs. This study may provide a new understanding of the mechanism of GC dysfunction.

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