Polimorfismos de la metilenotetrahidrofolato reductasa C677T como factor de riesgo para el síndrome de ovario poliquístico en una muestra de mujeres jordanas / Methylenetetrahydrofolate Reductase C677T Polymorphisms as a Risk Factor for Polycystic Ovarian Syndrome in a Sample of Jordanian Women

Antecedentes: el síndrome de ovario poliquístico (SOP) es un trastorno endocrino reproductivo común, se puede identificar por hiperandrogenismo, oligomenorrea o anovulación y ovarios poliquísticos en la ecografía. Los polimorfismos de la metilentetrahidrofolato reductasa (MTHFR) C677T asociados con la hiperhomocisteinemia se encuentran entre los factores de riesgo del síndrome de ovario poliquístico. Objetivo: El presente estudio de casos y controles tiene como objetivo explorar la relación entre los polimorfismos C677T de la metilenotetrahidrofolato reductasa (MTHFR) como factor de riesgo y el síndrome de ovario poliquístico entre los pacientes jordanos que padecen esta enfermedad. Métodos: Se inscribieron en el estudio 306 sujetos (146 pacientes con SOP y 160 sujetos sanos como grupo de control). Se extrajo ADN de una muestra de sangre venosa extraída de cada participante para analizar los polimorfismos de MTHFR C677T utilizando la reacción en cadena de la polimerasa (PCR) en combinación con digestión con enzima de restricción (PCRRFLP). Posteriormente, los productos de PCR-RFLP se digirieron con la enzima HinfI, luego se sometieron a electroforesis en un gel de agarosa al 2%, se tiñeron y se examinaron bajo luz ultravioleta. Los niveles de homocisteína en plasma se analizaron utilizando el método ELISA. Resultados: Se observó una diferencia significativa en los niveles plasmáticos de homocisteína entre los pacientes con SOP frente a los sujetos de control y entre los diferentes polimorfismos de los pacientes con SOP. No se detectaron diferencias significativas en la distribución y frecuencia alélica de los polimorfismos MTHFR C677T en pacientes con SOP en comparación con los controles. El genotipo 677 / TT y el alelo T se asociaron con un aumento de 1,54 y 1,46 veces en la susceptibilidad al síndrome de ovario poliquístico. Conclusión: El estudio ha demostrado que el polimorfismo MTHFR T677T y el alelo T son posibles factores de riesgo de SOP entre las mujeres jordanas y pueden desempeñar un papel en la patogenia de la enfermedad

Background: Polycystic ovary syndrome (PCOS) is a common endocrine reproductive disorder, it can be identified by hyperandrogenism, oligomenorrhea or anovulation and polycystic ovaries on ultrasound. Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphisms associated with hyperhomocysteinemia are among the risk factors for PCOS. Objective: The present case control study aims to explore the relationship between Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphisms as a risk factor and PCOS among Jordanian patients suffering from this disease. Methods: 306 subjects (146 PCOS patients and 160 healthy subjects as a control group) were enrolled in the study. DNA was extracted from venous blood sample withdrawn from each participant for analyzing MTHFR C677T polymorphisms using Polymerase Chain Reaction (PCR) in combination with restriction enzyme fragment length polymorphism (PCR-RFLP). Later, PCR-RFLP products were digested with hinfI enzyme, then, electrophoresed on a 2% agarose gel, stained and examined under UV light. Plasma homocysteine levels were assayed using ELISA method. Results: A significant difference was observed in plasma homocysteine levels among PCOS patients versus the control subjects and in between the different polymorphisms of PCOS patients. No significant difference was detected in the distribution and allelic frequency of MTHFR C677T polymorphisms in PCOS patients compared to the controls. 677/TT genotype and T allele were associated with 1.54 and 1.46 folds increase in the susceptibility for PCOS. Conclusion: The study has shown that MTHFR T677T polymorphism and T allele are possible risk factors for PCOS among Jordanian women and may play a role in the pathogenesis of the disease.

¿Existe una asociación entre polimorfismos de inserción/supresión - 2549 en la región promotora del gen que codifica la vegfa como factor de riesgo y el descargo espontáneo idiopático recurrente en una muestra de mujeres jordanas? / Is there an association between - 2549 Insertion/ Deletion Polymorphisms in the Promotor Region of the Gene Encoding for VEGFA as a Risk Factor and the Idiopathic Recurrent Spontaneous Miscarriage in a sample of Jordanian Women?

Antecedentes: al menos el 50% de los casos de aborto espontáneo recurrente son etiológicamente idiopáticos. Recientemente se han propuesto varios polimorfismos genéticos como factores de riesgo de susceptibilidad a la pérdida del embarazo. Objetivo: El objetivo del presente estudio de casos y controles es establecer la asociación entre los polimorfismos funcionales −2549 I / D en la región promotora del gen del factor de crecimiento endotelial vascular A (VEGFA) y el aborto espontáneo recurrente idiopático (IRSM) en una muestra de las mujeres jordanas. Sujetos y métodos: Se reclutaron 328 sujetos, 103 y 98 mujeres con IRSM primario y secundario, respectivamente, se seleccionaron 127 mujeres normales como grupo de control. Se aisló ADN genómico de una muestra de sangre extraída de cada participante, luego, se genotipificaron los polimorfismos I / D -2549 del gen VEGFA mediante la reacción en cadena de la polimerasa (PCR). Resultados: Los resultados obtenidos revelaron que el polimorfismo ID y el alelo D de VEGFA -2549 polimorfismos I / D tienen las frecuencias más altas en pacientes IRSM tanto primario como secundario, sin diferencia significativa entre los tres grupos en cuanto a polimorfismos y frecuencias alélicas, pacientes con DD + ID Los modelos genéticos tienen una asociación positiva con un alto riesgo de IRSM versus el modelo II, y los pacientes con alelo D son más propensos a tener IRSM que los que tienen el alelo I, no hay diferencia significativa en la asociación de polimorfismos VEGFA -2549 I / D con IRSM en los tres modelos genéticos de los pacientes con IRSM primario y secundario. Conclusión: los pacientes con modelo genético ID de polimorfismos I / D -2549 en la región promotora del gen VEGFA y el alelo D tienen mayor riesgo de IRSM

Background: At least 50% of the cases of recurrent spontaneous miscarriage are aetiologically idiopathic. Recently various genetic polymorphisms have been proposed as susceptibility risk factors for pregnancy loss. Objective: The aim of the present case control study is to establish the association between the functional −2549 I/D polymorphisms in the promoter region of the vascular endothelial growth factor A (VEGFA) gene and idiopathic recurrent spontaneous miscarriage (IRSM) in a sample of Jordanian women. Subjects and methods: 328 subjects were recruited, 103 and 98 women with primary and secondary IRSM, respectively, 127 normal women were selected as a control group. Genomic DNA was isolated from a blood sample withdrawn from each participant, then, -2549 I/D polymorphisms of VEGFA gene were genotyped by Polymerase Chain Reaction (PCR). Results: The obtained results revealed that ID polymorphism and D allele of VEGFA -2549 I/D polymorphisms have the highest frequencies in both primary and secondary IRSM patients, no significant difference between the three groups regarding polymorphisms and allele frequencies, patients with DD+ID genetic models have positive association with high risk of IRSM versus II model, and patients with D allele are more liable to have IRSM than those having I allele, no significant difference in the association of VEGFA -2549 I/D polymorphisms with IRSM in the three genetic models of the primary and secondary IRSM patients. Conclusion: patients with ID genetic model of -2549 I/D polymorphisms in the VEGFA gene's promotor region and D allele have higher risk for IRSM.

Effects of progesterone and estradiol on the inflammatory and apoptotic markers of ovariectomized rats challenged with acute septic systemic inflammation

The inflammatory responses during septic inflammation were affected by the differential role of progesterone and estrogen that demonstrated pro-inflammatory and anti-inflammatory roles. This study was designed to evaluate the differential effects of estradiol and progesterone supplementation on the inflammatory and apoptotic responses in an ovariectomized (OVX) rat model of acute systemic septic inflammation (SSI). This study was conducted on 60 female Wistar rats. 40 mg/kg estradiol and 5 mg/kg progesterone were given subcutaneous (s.c.) to OVX rats, after the induction of SSI through caecum puncture with a 21-gauge needle. Serum levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), Alanine transaminase (ALT), estradiol, and progesterone were evaluated; additionally, Inducible nitric oxide synthase (iNOS), Cyclooxygenase (COX)-II, and caspase-3 were evacuated in liver tissue homogenates using the Enzyme-linked immunosorbent assay (ELISA) method. In OVX rats challenged with SSI, serum TNF-α, CRP, and ALT levels were significantly increased associated with a decrease in serum estradiol levels. They also showed overexpression of iNOS and increased the activity of COX-II and caspase-3 in the liver compared to non-OVX rats subjected to SSI. Supplementation with estradiol significantly decreases all serum and liver tissue markers of inflammation and decreased apoptosis. In contrast, in OVX rats supplemented with progesterone, SSI resulted in a significant increase in the studied markers. In conclusion, the supplementation of estradiol in OVX rats challenged with SSI significantly attenuated the systemic and liver inflammatory and apoptotic markers. Meanwhile, the supplementation with progesterone exacerbates the effects of the inflammatory markers and increases the tendency of apoptosis in the liver tissue.

Plasma Thrombopoietin Level in Thrombocytopenic Patients with or without Liver Cirrhosis Chronically Infected By the Hepatitis C Virus.

Background and Aim: Thrombocytopenia is a frequent problem in patients with post- hepatitis C (HCV) liver cirrhosis and also occurs in chronic HCV-infected patients without liver cirrhosis. The aim of this study was to evaluate the role of plasma thrombopoietin (TPO) in the occurrence of thrombocytopenia in both conditions. Method: Platelet count and plasma thrombopoietin level and liver function tests were measured in four groups of patients: twenty chronic patients with post-hepatitis C liver cirrhosis and thrombocytopenia (group I), ten chronic HCV-positive patients with liver cirrhosis without thrombocytopenia (group II), ten chronic HCV-positive patients without liver cirrhosis with thrombocytopenia (group III) and chronic ten HCV-positive patients without liver cirrhosis and without thrombocytopenia (group IV). Ten normal healthy individuals were included as a control group. Results: Plasma levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), TPO and platelet counts in the four groups of patients were significantly different from their corresponding levels in the control group (P <0.001). There was a significant positive correlation between plasma TPO levels and platelet counts in group III patients (ρ (Spearman's [rho]) = 0.661, P= 0 .038). There was no significant correlation between TPO levels and platelet counts in the other three groups of patients. The logistic regression analysis in the three designated models, using dependent variables (chronic HCV infection, liver cirrhosis and thrombocytopenia) and an independent variable (TPO plasma level) revealed that liver cirrhotic patient and the thrombocytopenic patient have equally the best prediction model for the low plasma TPO. Conclusion: Decreased thrombopoietin production has a role in the pathogenesis of thrombocytopenia in liver cirrhosis.

Carcinogen Metabolizing Enzymes: Modulation of Their Activities in Liver, Lung and Stomach by Thymoquinone.

Background: Thymoquinone (TQ), the bioactive constituent of black seed (Nigella sativa), has been shown to inhibit the growth of various human cancerous cells both in vitro and in vivo. Aim: To characterize the effects of thymoquinone on the activity of phase I and phase II carcinogen metabolizing enzymes in rats. Materials and Methods: Phase I enzymes, namely the cytochrome P450 enzymes CYP1A1 and CYP2E1, and phase II enzymes, including UDP-glucuronyltransferase (UGT) and glutathione S-transferase (GST), were studied in the liver, lung and stomach of female Swiss albino rats. The animals were divided into two groups (10 rats/group), a control group treated with corn oil and a TQ-treated group receiving oral (gavage) thymoquinone at a dose of 10 mg/kg/day for 15 consecutive days. Animals were then sacrificed on day 16. Tissue homogenates of liver, lung and stomach were prepared to evaluate the activities of both phase I and phase II selected enzymes. Results: Thymoquinone treatment induced significant modulation of the selected phase I and phase II enzymes in a tissue-specific manner. Our results revealed statistically significant reductions in the activities of CYP1A1 enzyme (46%, 60% and 57% in liver, lung and stomach respectively) versus the control group. Similarly, CYP2E1 activities were decreased in both liver and lung, by 51% and 16%, respectively, compared to the control group. UGT enzyme showed a decrease of 51% in liver, but a significant rise in both lung and stomach, by 40% and 192%, respectively. GST activity, on the other hand, was moderately enhanced, by 24%, 50% and 30% in liver, lung and stomach, respectively. Conclusion: Thymoquinone, in addition to scavenging active metabolites of chemical carcinogens, may also change their metabolisms by modulating the activity levels of enzymes involved in carcinogen activation and/or xenobiotics pathways.