Impacts of RETN genetic polymorphism on breast cancer development in Beni-Suef females, Egypt.

Breast cancer is the most common cancer among females with increasing incidence and death rates. Resistin is pro-inflammatory molecule which shares in diverse cellular signaling pathways. This study aimed to evaluate resistin and RETN rs3219175 gene polymorphism and their relevance to diagnostic susceptibility, prognostic value, and genetic risk among Egyptian female patients with breast cancer. Eighty female patients with breast cancer were recruited from the Oncology Department, Faculty of Medicine, Beni-Suef University. Breast cancer staging and grading were determined. Eighty age-matched normal females participated as controls. Quantitative determination of serum resistin was assayed by an enzyme-linked immunosorbent assay (ELISA). RETN rs3219175 gene polymorphism was determined by real time polymerase chain reaction (RT-PCR) TaqMan allelic discrimination assay. Serum resistin showed statistically significantly higher level among females with breast cancer when compared to controls (p < 0.001). Resistin showed sensitivity of 80% and specificity of 67.5% at cut off value of 1.27 ng/mL for diagnosis of breast cancer (p =0.001). RETN rs3219175 gene polymorphism showed significantly higher frequency of AG, AA genotypes, and A allele among cases when compared to controls (p < 0.001). No statistical difference was found in resistin level or RETN rs3219175 gene polymorphism regarding tumor characteristics including size, lymph nodes or distant metastasis. Resistin showed significantly higher level among carriers of AG followed by AA genotypes and among A allele (p < 0.001). In conclusion, resistin could be proposed as a possible potential diagnostic marker and A allele of RETN rs3219175 gene might be suggested as a genetic risk allele among female patients with breast cancer.

Estimation of Serum and Seminal Plasma Levels of Glactin-1 in Non-Obstructive Azoospermia Cases and Their Correlations with the Rate of Sperm Retrieval: A Comparative Prospective Study.

Background: Remarkably, the current study is one of the first to deploy galectin-1 (Gal-1) in determining the degree of impairment of spermatogenesis among cases with non-obstructive azoospermia (NOA) as well as utilizing it as a biomarker to predict the rate of sperm retrieval in these patients. The purpose of the study was to evaluate the seminal plasma and serum levels of Gal-1 in NOA patients as well as their correlations with Johnsen's tubular biopsy scoring (JTBS). Methods: The current case control study included totally 48 patients with NOA whose ages ranged from 24 to 46 years old and 50 age matched healthy controls. Gal-1 levels were measured in both seminal plasma and serum of all subjects by the enzyme-linked immunosorbent assay (ELISA). Results: A significant negative correlation between seminal plasma levels of Gal-1 and JTBS was detected (r= -0.281, p=0.048) in the NOA cases. Interestingly, the receiver operating characteristic (ROC) curve had demonstrated that the cutoff value of seminal plasma levels of Gal-1 in determining azoospermia was >0.735 ng/ml and the area under the curve (AUC) was 0.858. The sensitivity, specificity, positive predictive, and negative predictive values for seminal plasma levels of Gal-1 were 76, 92, 90.5, and 79.3, respectively. In addition, sensitivity, specificity, positive predictive, and negative predictive values for serum levels of Gal-1 were 38, 66, 52.8, and 51.6, respectively. Conclusion: Seminal plasma levels of Gal-1 are higher in NOA men versus healthy controls. Interestingly, negative correlation of seminal plasma levels of Gal-1 with JTBS was determined. Thus, it can be used as a good predictor for NOA cases.

An association between the sarcolemmal membrane-associated protein gene and microvascular endothelial diabetic retinopathy in patients with type 2 diabetes mellitus: A preliminary case control study.

BACKGROUND AND AIMS: Diabetic retinopathy (DR) is one of the most common microvascular diabetic complications. Sarcolemmal membrane-associated protein (SLMAP) has been implicated in playing a role in microvascular endothelial dysfunction. This study aimed to assess the significance of SLMAP rs17058639C > T gene polymorphism among patients with type 2 diabetes mellitus (T2DM) and its relevance to microvascular endothelial diabetic retinopathy. METHODS: We conducted this case-control study on 100 individuals divided into 60 participants with T2DM and 40 healthy controls. Patients with T2D were stratified into two groups: 40 patients with DR and 20 patients with diabetic non-retinopathy (DNR). Patients with T2DM were compared with age- and sex-matched healthy controls. Fundus examinations were conducted to detect microvascular endothelial changes. The polymorphism of SLMAP rs17058639C > T gene was identified by real-time polymerase chain reaction (RT-PCR) TaqMan allelic discrimination. RESULTS: Patients with DR have significantly increased glycated hemoglobin (HbA1c) compared to patients with DNR (P < 0.001). There was no statistically significant difference found between diabetic and control groups regarding the frequency of SLMAP rs17058639C > T genotypes. The homozygous CC genotype was the most common variant among patients with DR; however, the results did not reach statistical significance. CONCLUSIONS: Diabetic retinopathy is correlated with poor glycemic control, and SLMAP rs17058639C > T polymorphism was associated with microvascular endothelial DR in patients with T2DM, although further studies with a large sample size are needed to confirm our findings.

Seminal L-Carnitine In Infertile Oligoasthenoteratozoospermic Men with Varicocele.

Background: Few studies have investigated the relationship of seminal L-Carnitine (LC) with male infertility associated with varicocele. The purpose of this prospective cross-sectional study was to assess seminal plasma LC levels in infertile oligoathenoteratozoospermic (OAT) men with varicocele. Methods: Overall, 86 men were investigated. They were divided into infertile OAT men with varicocele (n=45), infertile OAT men without varicocele (n=21), and fertile men (n=20) as a control group. According to WHO guidelines, these men were subjected to history taking, clinical examination, and semen analysis. Seminal LC levels were evaluated by the colorimetric method. Statistical comparisons were done using Kruskal-Wallis and Mann-Whitney U tests and correlations were verified by the Pearson test. P-value<0.05 was set to be statistically significant. Results: The mean seminal plasma LC levels were significantly lower in infertile OAT men with varicocele (216.3±57.1 ng/ml) compared to infertile OAT men without varicocele (252.9±62.9 ng/ml, p=0.01), or fertile men (382.8±63.6 ng/ml, p=0.001). Besides, the mean seminal plasma LC level exhibited statistically significant decreases in infertile OAT men of varicocele grade III compared to varicocele grade II cases, and in infertile OAT men with bilateral varicocele compared with unilateral varicocele cases. Collectively, there was a statistically significant positive correlation between seminal LC levels with sperm concentration, motility, and normal morphology. Conclusion: Seminal LC levels are expressively reduced in infertile OAT men with varicocele and are influenced by an increase in varicocele grade and laterality.

Disheveled EGL-10 and pleckstrin domain-containing 5 rs1012068 T/G gene polymorphism among Egyptian chronic HCV-infected patients: disease progression and related complications.

Hepatitis C virus (HCV) infection related complications including fibrosis, cirrhosis and hepatocellular carcinoma (HCC) are influenced by host genetic factors. Identification of emerging host genetic variations is of promising value. Disheveled EGL-10 and pleckstrin domain-containing 5 (DEPDC5) rs1012068 T/G gene polymorphism has been implicated in liver disease. This study aimed to assess DEPDC5 rs1012068 T/G gene polymorphism with disease progression and related complications among Egyptian patients with chronic HCV infection. Sixty chronic HCV-infected patients and 60 apparently healthy controls were recruited in this study. Patients were classified into 20 with liver fibrosis, 20 with liver cirrhosis and 20 with HCC; all recruited from Outpatients Clinic and Tropical Medicine Inpatient Department, Faculty of Medicine, Beni-Suef University Hospital. DEPDC5 rs1012068 T/G gene polymorphism was assayed by real time-polymerase chain reaction (RT-PCR) TaqMan allelic discrimination. DEPDC5 rs1012068 GG genotype and G allele variants showed statistically significant higher frequency among patients with liver fibrosis when compared to controls (OR (95% CI) 10.500 (2.086 - 52.851), P= 0.004 and 0.388 (0.155 - 0.971), P= 0.011), respectively. DEPDC5 rs1012068G allele variant showed statistically significant higher frequency among patients with liver fibrosis when compared to HCC patients (OR (95% CI) 3.316 (1.286 - 8.550), P= 0.012) and to both HCC and cirrhosis patients (OR (95% CI) 2.579 (1.187-5.645), P= 0.016). In conclusion, our results suggest that DEPDC5 rs1012068 G allele could be considered genetic risk allele for liver fibrosis and disease progression among Egyptian patients with chronic HCV infection.

Assessment of seminal calcium and magnesium levels in infertile men with varicocele before and after varicocelectomy.

BACKGROUND: Trace elements perform a vital role in all stages of human physiology, as well as reproduction. OBJECTIVE: This study aimed to assess seminal calcium (Ca) and magnesium (Mg) in infertile men associated with varicocele (Vx). MATERIALS AND METHODS: Overall, 50 men were divided into two groups: fertile men (n = 20) and infertile men who were scheduled for Vx surgical repair (n = 30). Exclusion criteria were as follows: azoospermia, smoking, leukocytospermia, and consumption of Ca and/or Mg supplements. All cases were subjected to history taking and clinical examination. Semen analysis and assessment of seminal Ca and Mg by the colorimetric method were carried out for all cases at the base point and 3 months postvaricocelectomy. RESULTS: Generally, the mean seminal Ca and Mg levels demonstrated significant decreases in infertile men with Vx compared with the healthy fertile men linked to higher Vx grade as well as Vx bilaterality. These seminal decreases demonstrated significant increases after Vx surgical repair. Collectively, seminal Ca and Mg levels showed a significant positive correlation (r = 0.665, p= 0.001). Besides, seminal Ca, Mg levels, and Ca/Mg ratio showed significant positive correlation with sperm concentration (r = 0.479, p = 0.001; r = 0.541, p = 0.001; r = 0.282, p = 0.001, respectively), sperm motility percentage (r = 0.493, p = 0.001; r = 0.477, p = 0.001; r = 0.353, P = 0.001, respectively), and sperm normal forms percentage (r = 0.578, p = 0.001; r = 0.520, p = 0.001; r = 0.430, p = 0.001, respectively). DISCUSSION AND CONCLUSION: Seminal Ca and Mg levels and Ca/Mg ratio are significantly decreased in infertile men associated with Vx compared with fertile men with significant increases after varicocelectomy.

Evaluation of stromal cell-derived factor-1ß Gene polymorphism G801A among Egyptian patients with type 2 diabetes mellitus.

Stromal cell derived factor - 1 (SDF-1) is expressed by bone marrow derived stromal cells and stromal tissues in multiple organs. SDF-1 possesses diverse physiological and biochemical functions concerning autoimmunity and inflammation. SDF-1 gene polymorphisms play various roles in immune related diseases. This study aimed to evaluate association of SDF-1ß G801A gene polymorphism and type 2 diabetes mellitus (T2DM) as regard prevalence and glycemic control. The study included hundred Egyptian subjects; 50 patients with T2DM recruited from the Internal Medicine Department, Beni-Suef University Hospital, and 50 age and sex matched healthy subjects. Participants were subjected to full clinical examination and routine laboratory investigations including fasting blood glucose, 2 hours post prandial blood glucose, serum creatinine, lipid profile and glycated hemoglobin (HbA1c). SDF-1ß G801A gene polymorphism was analyzed using polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP). The frequency of GG and AG genotypes was higher in patients compared to controls with no statistical significance. Higher frequency of homozygous GG genotype and G allele were observed among patients with poor glycemic control (HbA1c ≥ 8% ) compared to those with good glycemic control (HbA1c < 8%) (P = 0.001 and 0.018 respectively). In conclusion, this study suggested an association between SDF-1 ß gene polymorphism and type 2 diabetes mellitus in Egyptian patients. Further studies are needed to confirm our observations.

Vascular endothelial growth factor C/A 2578 gene polymorphism and umbilical artery Doppler in preeclamptic women.

INTRODUCTION: Preeclampsia is strongly associated with placental hypoperfusion. Genetic factors have an impact on the pathogenesis of preeclampsia. The aim is to assess the association of Vascular Endothelial Growth Factor (C2578A) gene polymorphism with the occurrence and severity of preeclampsia and the umbilical artery Doppler changes among preeclamptic women. MATERIALS AND METHODS: This case-control study was conducted in clinical and Chemical pathology and Obstetrics departments in Beni- Suef University, Egypt. Two hundred and ninety pregnant women above 20 weeks gestational age until delivery were divided into 2 main groups. The patient group included 145 preeclamptic women who were further sub grouped according to the severity of preeclampsia into 82 severe and 63 mild cases. Control group included 145 normotensive pregnant women. Our primary outcome was detection of VEGF C 2578 A gene mutations by a polymerase chain reaction. A secondary outcome was Doppler changes in the pulsatility index of the umbilical artery compared with VEGF genotypes. RESULTS: Our study showed that VEGF C 2578 A genotype and alleles frequencies were not related to the occurrence of preeclampsia (p-value 0.513 and 0.549, respectively), odds ratio (95%CI) 1.154 (0.724-1.848). Mild preeclamptic cases showed no significance comparing VEGF genotypes studied and pulsatility index of the umbilical artery. However, severe cases showed p-value < 0.0001. CONCLUSION: We concluded that VEGF 2578C/A polymorphism had no association with the occurrence of preeclampsia in studied groups, whereas there was a significant relationship among severe cases between CA and CC genotypes and pulsatility index of the umbilical artery.

Aryl hydrocarbon receptor (AhR) rs2066853 gene polymorphism association with infertile oligoasthenoteratozoospermic men and seminal oxidative stress.

This study aimed to assess the association between aryl hydrocarbon receptor (AhR) rs2066853 gene polymorphism with infertile oligoasthenoteratozoospermic (OAT) men and seminal oxidative stress (OS). A total of 170 Egyptian men were allocated according to their semen analysis into fertile normozoospermic controls (n = 50) and infertile OAT men (n = 120). They were subjected to history taking, clinical examination, semen analysis, estimation of seminal glutathione peroxidase (GPx), and malondialdehyde (MDA). AhR rs2066853 gene polymorphism was identified in the blood by PCR-RFLP. Comparing infertile OAT men with fertile controls, AhR rs2066853 genotypes showed decreased prevalence for wild homozygous genotype GG (35.8 vs 56%) and for heterozygous genotype GA (17.5 vs 30%) and an increased prevalence for homozygous genotype AA (46.7 vs 14%). Distribution of alleles of AhR rs2066853 among OAT men compared with fertile men showed decreased prevalence of G allele (44.6 vs 71%) and an increased prevalence of A allele (55.4 vs 29%). Seminal MDA demonstrated significant increase whereas seminal GPx demonstrated significant decrease in cases with AA and GA/AA genotypes compared to cases with GG genotype. It is concluded that there is a significant association between AhR rs2066853 genotype polymorphism with decreased sperm parameters as well as increased seminal oxidative stress in infertile OAT men.