scholarly journals Association of the Apolipoprotein E 2 Allele with Concurrent Occurrence of Endometrial Hyperplasia and Endometrial Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Tatiana I. Ivanova ◽  
Ludmila I. Krikunova ◽  
Nikolay I. Ryabchenko ◽  
Liana S. Mkrtchyan ◽  
Vera A. Khorokhorina ◽  
...  

Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n= 89), EH concurrent with ECa (n= 76), ECa (n= 186), and healthy controls (n= 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOECys112Arg and Arg158Cys), iron (HFECys282Tyr and His63Asp), and catecholamines (COMTVal158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes. The frequency of theAPOEE 2 allele (158Cys) was higher in patients with EH + ECa than in controls (P= 0.0012,PBonferroni= 0.018, OR = 2.58, 95% CI 1.49–4.45). TheAPOEE 4 allele (112Arg) was more frequently found in patients with EH than in controls andHFEminor allele G (63Asp) had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa.

2008 ◽  
Vol 24 (2) ◽  
pp. 81-88 ◽  
Author(s):  
Anna Balcerzyk ◽  
Iwona Zak ◽  
Jolanta Krauze

Background: Genetic susceptibility to CAD may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipids disorders. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background.Aim: The aim of the study was an evaluation a possible association between single polymorphic variants ofPON1, APOE, ABCA1andPPARAgenes and CAD and looking for specific multigene genotype patterns which differentiate study groups.Materials and methods: We studied 358 subjects:178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using PCR-RFLP method.Results: We observed statistically significant differences in the frequencies of R allele and R allele carriers ofPON1gene between CAD and controls. The distribution of genotypes and alleles of other analyzed genes did not differentiate the study groups, however the presence of specific genotypes (APOE– ɛ3ɛ3, ɛ3ɛ2,ABCA1– AG,PPARA– GG) increased the protective effect of R allele.Conclusion: The present study revealed an independent protective association between carrier-state of PON1 R allele and CAD. This protective effect was especially strong in the presence of specific genotype arrangements of other analyzed genes.


2021 ◽  
Vol 22 (16) ◽  
pp. 8805
Author(s):  
Egor A. Turovsky ◽  
Elena G. Varlamova ◽  
Egor Y. Plotnikov

Ischemia-like conditions reflect almost the entire spectrum of events that occur during cerebral ischemia, including the induction of oxidative stress, Ca2+ overload, glutamate excitotoxicity, and activation of necrosis and apoptosis in brain cells. Mechanisms for the protective effects of the antioxidant enzyme peroxiredoxin-6 (Prx-6) on hippocampal cells during oxygen-glucose deprivation/reoxygenation (OGD/R) were investigated. Using the methods of fluorescence microscopy, inhibitory analysis, vitality tests and PCR, it was shown that 24-h incubation of mixed hippocampal cell cultures with Prx-6 does not affect the generation of a reversible phase of a OGD-induced rise in Ca2+ ions in cytosol ([Ca2+]i), but inhibits a global increase in [Ca2+]i in astrocytes completely and in neurons by 70%. In addition, after 40 min of OGD, cell necrosis is suppressed, especially in the astrocyte population. This effect is associated with the complex action of Prx-6 on neuroglial networks. As an antioxidant, Prx-6 has a more pronounced and astrocyte-directed effect, compared to the exogenous antioxidant vitamin E (Vit E). Prx-6 inhibits ROS production in mitochondria by increasing the antioxidant capacity of cells and altering the expression of genes encoding redox status proteins. Due to the close bond between [Ca2+]i and intracellular ROS, this effect of Prx-6 is one of its protective mechanisms. Moreover, Prx-6 effectively suppresses not only necrosis, but also apoptosis during OGD and reoxygenation. Incubation with Prx-6 leads to activation of the basic expression of genes encoding protective kinases—PI3K, CaMKII, PKC, anti-apoptotic proteins—Stat3 and Bcl-2, while inhibiting the expression of signaling kinases and factors involved in apoptosis activation—Ikk, Src, NF-κb, Caspase-3, p53, Fas, etc. This effect on the basic expression of the genome leads to the cell preconditions, which is expressed in the inhibition of caspase-3 during OGD/reoxygenation. A significant effect of Prx-6 is directed on suppression of the level of pro-inflammatory cytokine IL-1β and factor TNFα, as well as genes encoding NMDA- and kainate receptor subunits, which was established for the first time for this antioxidant enzyme. The protective effect of Prx-6 is due to its antioxidant properties, since mutant Prx-6 (mutPrx-6, Prx6-C47S) leads to polar opposite effects, contributing to oxidative stress, activation of apoptosis and cell death through receptor action on TLR4.


2021 ◽  
Vol 10 (13) ◽  
pp. 2811
Author(s):  
Katarzyna Ożegowska ◽  
Szymon Plewa ◽  
Urszula Mantaj ◽  
Leszek Pawelczyk ◽  
Jan Matysiak

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine and metabolic disorder, affecting 5–10% of women of reproductive age. It results from complex environmental factors, genetic predisposition, hyperinsulinemia, hormonal imbalance, neuroendocrine abnormalities, chronic inflammation, and autoimmune disorders. PCOS impacts menstrual regularities, fertility, and dermatological complications, and may induce metabolic disturbances, diabetes, and coronary heart disease. Comprehensive metabolic profiling of patients with PCOS may be a big step in understanding and treating the disease. The study aimed to search for potential differences in metabolites concentrations among women with PCOS according to different body mass index (BMI) in comparison to healthy controls. We used broad-spectrum targeted metabolomics to evaluate metabolites’ serum concentrations in PCOS patients and compared them with healthy controls. The measurements were performed using high-performance liquid chromatography coupled with the triple quadrupole tandem mass spectrometry technique, which has highly selective multiple reaction monitoring modes. The main differences were found in glycerophospholipid concentrations, with no specific tendency to up-or down-regulation. Insulin resistance and elevated body weight influence acylcarnitine C2 levels more than PCOS itself. Sphingomyelin (SM) C18:1 should be more intensively observed and examined in future studies and maybe serve as one of the PCOS biomarkers. No significant correlations were observed between anthropometric and hormonal parameters and metabolome results.


2020 ◽  
Vol 19 ◽  
pp. 153303382096558
Author(s):  
Lixia Shan ◽  
Tao Zhao ◽  
Yu Wang

Objective: Long non-coding RNAs (lncRNAs) play a critical role in tumorigenesis. Upregulation of lncRNA deleted in lymphocytic leukemia 1 (DLEU1) has been reported in endometrial cancer (EC) tissues. This prospective study aimed to determine the potential clinical significance of serum lncRNA DLEU1 in EC. Methods: The serum lncRNA DLEU1 level was detected in EC patients, patients with endometrial hyperplasia and healthy controls by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then its clinical value in EC was further evaluated. Results: Our results demonstrated that serum lncRNA DLEU1 levels were significantly increased in patients with EC, and serum lncRNA DLEU1 showed good performance for discriminating EC patients from patients with endometrial hyperplasia and healthy controls. In addition, EC patients with advanced clinicopathological features had higher circulating lncRNA DLEU1 level than those with favorable clinical characteristics. Moreover, EC patients in the high serum lncRNA DLEU1 group suffered worse overall survival and disease-free survival than those in the low serum lncRNA DLEU1 group. Furthermore, multivariate cox regression analysis displayed that the serum lncRNA DLEU1 served as an independent prognostic factor for EC. Conclusions: Collectively, our study suggests that serum lncRNA DLEU1 is a novel and promising biomarker for prognostic estimation of EC.


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