Association between genetic variants of GRM7 (rs1396409 and rs9883258) and treatment outcomes in Schizophrenic Egyptian patients.

BACKGROUND AND AIM: This study evaluated the association between rs1396409 and rs9883258 and the risk of schizophrenia (SCZ) and treatment outcomes in Egyptian patients. METHODS: This study included 88 patients with SCZ and 88 healthy controls. Lipid profile was assayed. Genotyping of rs1396409 and rs9883258 polymorphisms was analyzed using real-time PCR. RESULTS: The rs1396409 AG genotype frequency was significantly associated with SCZ risk (p = 0.002). Also, significant increased risk of SCZ was observed under allelic (p = 0.001), dominant (p = 0.001) and overdominant (p = 0.001) genetic model of rs1396409. However, rs9883258 AA genotype revealed nonsignificant association with SCZ. Cases with the rs1396409AG genotype exhibited hypertriglyceridemia (p < 0.001) and hypercholesterolemia (p = 0.001). In total, 72.3% and 74.5% of the cases presented with rs1396409 AG have negative symptoms (p = 0.022) and exhibited poor drug response (p = 0.023), respectively; all cases with rs1396409 GG genotype attempted suicide (p = 0.002) and are drug-free (p = 0.003). SCZ patients with negative symptoms had hypercholesterolemia (p = 0.008) mainly low-density lipoproteins (LDLc) (p = 0.016), and those with cognitive symptoms presented with low level of high-density lipoprotein (HDLc) (p = 0.023). Moreover, the multivariate regression analysis revealed that both rs1396409 G allele and HDLc were predictors of SCZ (p = 0.003 and 0.001, resp.). CONCLUSION: The current study concluded that metabotropic glutamate receptor 7 (GRM7) rs1396409 AG could be a potential biomarker for SCZ diagnosis. It also revealed an independent association between the GRM7 rs1396409 G allele, HDLc and SCZ development.

Expression profile of long-noncoding RNAs MIR31HG, NKILA, and PACER in systemic lupus erythematosus patients.

OBJECTIVES: Growing evidence suggests that systemic lupus erythematosus (SLE), an organ-damaging systemic autoimmune illness, may be influenced by long-noncoding RNAs (lncRNAs). This study aimed to assess the relative expression of lncRNAs (MIR31HG, NKILA, and PACER) in patients with SLE to evaluate their role in the disease. DESIGN AND METHODS: This study involved 70 patients with SLE and 70 apparently healthy control subjects. The expression levels of lnc-MIR31HG, NKILA, and PACER were quantified using real-time PCR. RESULTS: Lnc-MIR31HG, NKILA, and PACER were significantly upregulated in SLE cases compared to controls (P < 0.001). ROC curve analysis revealed a 91.43 % sensitivity of PACER for the diagnosis of SLE at a cutoff point of > 1.46, followed by NKILA with 90 % sensitivity at a cutoff point of > 1.16, and MIR31HG with 85.71 % sensitivity at a cutoff point of > 1.43. MIR31HG had the highest sensitivity for the diagnosis of lupus nephritis (86.67 %) at a cutoff point of > 7.19, then NKILA with 80 % sensitivity at a cutoff point of > 8.12, and finally PACER expression with 73.33 % sensitivity at a cutoff point of > 18.19. Moreover, MIR31HG and NKILA revealed a significant correlation with albumin/creatinine ratio, estimated glomerular filtration rate, and the SLEDAI score. Regression analysis revealed the potential roles of MIR31HG, NKILA, and PACER expression as predictors for SLE. CONCLUSION: An upregulated lncRNA panel (MIR31HG, NKILA, and PACER) could play a role in the pathogenesis and, hence, the predispositiontoSLE. MIR31HG and NKILA can serve as prognostic markers significantly linked with disease activity.

Impact of Dysregulated LINC01559 and LINC01410 Expression on the Diagnosis and Survival of Non-Small Cell Lung Cancer.

Lung cancer is a widely recognized cancer with a very low survival rate, as it is mostly diagnosed at advanced stages. The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC). LncRNAs are widely involved in cancer progression and migration. Therefore, we intended to estimate the circulatory expression levels of LINC01559 and LINC01410 in NSCLC and their roles in tumor prognosis evaluation as less invasive potential markers. The relative expression levels of the plasma cell-free lncRNAs LINC01559 and LINC01410 in seventy patients with NSCLC and seventy healthy subjects as controls were measured by real-time PCR. Enzyme-linked immunosorbent assays were utilized to measure carcinoembryonic antigen (CEA) concentrations. The LINC01559 and LINC01410 expression levels were significantly increased in NSCLC patients versus controls. Both lncRNAs showed good performance in the ROC curve analysis with high sensitivity and specificity for distinguishing patients from controls. LINC01559 had the highest AUC in the ROC curve analysis (0.96, 95 CI% CI: 0.93-0.99) for distinguishing patients from controls, while LINC01410 had the highest AUC (0.77, 95 CI% CI: 0.65-0.89) for differentiating metastatic tumors from nonmetastatic tumors. High expression levels of LINC01410 and LINC01559 were associated with low overall survival (log rank = 47.04 and 28.18, respectively, P < 0.001) and low progression-free survival (log rank = 40.68 and 28.77, respectively (P < 0.001)) and with the presence of metastasis. We suggest that LINC01559 and LINC01410 can be used as valuable, high-performing biomarkers in NSCLC diagnosis and prognosis prediction.

Evaluation of the expression levels of lncRNAs H19 and MEG3 in patients with type 2 diabetes mellitus.

BACKGROUND: LncRNAs may play a role in either suppressing or exacerbating diabetes-associated vascular complications. AIMS: This study aimed to assess MEG3 and H19 expression levels in T2DM and pre-diabetes and their roles in diabetes-related microvascular complications. SUBJECT AND METHODS: (RT-PCR) analysis of the MEG3 and H19 plasma levels was carried out in 180 participants of T2DM, pre-diabetes, and control. RESULTS: The expression level of lncRNA H19 was significantly down-regulated and lncRNA MEG3 up-regulated in T2DM compared to pre-diabetes and control, also for pre-diabetes versus control. The (ROC) analysis of MEG3 and H19 relative expression levels showed that MEG3 has better sensitivity for distinguishing T2DM from pre-diabetes and control groups.In comparison, H19 offered superior sensitivity to distinguish pre-diabetic from controls. Additionally, H19 was reported as an independent risk factor for T2DM by multivariate analysis. Low expression of H19 and over-expressed MEG3 were significantly associated with retinopathy, nephropathy, and elevated renal indicators (urea, creatinine, and UACR. CONCLUSION: Our results implicated the potential diagnostic and predictive roles of lncRNA MEG3 and H19 for T2DM and related microvascular complications. Additionally, H19 may serve as a potential biomarker for pre-diabetes prediction.

Various Expressions of PIK3C2A and TXNIP Genes and Their Potential Role as Independent Risk Factors for Chronic Stable Angina and Acute Coronary Syndrome.

BACKGROUND AND AIM: Genetic factors play a significant role in the onset and progression of coronary artery disease (CAD). PIK3C2A may contribute to the development of acute coronary syndrome (ACS) by affecting blood glucose levels and oxidative stress. The expression levels of TXNIP were significantly higher in patients with unstable angina pectoris. However, the situation is different in ACS. In the current study, we aim to investigate the role of PIK3C2A and TXNIP as independent risk factors for chronic stable angina (CSA) and ACS. SUBJECTS AND METHODS: This study involved 215 subjects (60 patients with CSA, 55 patients with ACS, and 100 controls). All subjects were exposed for assaying gene expressions of PIK3C2A and TXNIP by quantitative real-time polymerase chain reaction. RESULTS: It was found that TXNIP was upregulated, whereas PIK3C2A was downregulated in patients with CAD compared to the control group. PIK3C2A was significantly downregulated in patients with ACS compared to that in patients with CSA (p < 0.001), but TXNIP was not (p = 0.7). TXNIP was significantly upregulated in STEMI-ACS patients compared to CSA (p = 0.045) and NSTEMI ACS (p = 0.046), among non-diabetic (p = 0.023) smokers (p = 0.036) with hypertension (p = 0.005) and hypercholesterolemia (p = 0.001). ROC (receiver operating characteristic) curve analysis revealed that PIK3C2A (0.981; p < 0.001; 98.18) was the most sensitive mRNA for discriminating ACS from control, followed by TXNIP (0.775; p < 0.001; 70.91). However, for discriminating ACS from CSA combined mRNAs, (PIK3C2A + TXNIP) (0.893; p < 0.001; 98.18) and PIK3C2A (0.892; p < 0.001; 81.82) are promising biomarkers. On the other hand, the most sensitive mRNA for differentiating CSA from control is mRNAs (PIK3C2A + TXNIP) (0.963; p < 0.001; 95), then TXINP (81.3; p < 0.001; 93.33), and finally, PIK3C2A (0.782; p < 0.001; 81.67). In the multivariate regression model, PIK3C2A ((p = 0.002), 0.118 (0.031-0.445)) and smoking status ((p = 0.034); 0.151 (0.026-0.866)) were independent variables for ACS. Moreover, PIK3C2A ((p < 0.013); 0.706 (0.614-0.812)), Hb ((p = 0.013); 0.525 (0.317-0.871)), and total cholesterol ((p = 0.04); 0.865 (0.784-0.955)) were significantly (p < 0.05) and independently related to the prognosis of CSA. Furthermore, PIK3C2A ((p = 0.002), 0.923 (0.877-0.971)), TXNIP ((p = 0.001); 2.809 (1.558-5.064)) the body weight ((p = 0.033); 1.254 (1.018-1.544)) were independently associated with CSA. CONCLUSIONS: Our study concluded that the dysregulated mRNA PIK3C2A and TXNIP gene expressions may be useful in diagnosis of CAD and prediction of ACS development.

Impact of Helicobacter pylori on hematological parameters among Saudi population.

OBJECTIVES: To investigate prevalence and association between iron deficiency anemia (IDA) and Helicobacter pylori (H. pylori). METHODS: This cross-sectional study included 79 participants with unexplained IDA. The study was carried out between November 2018 to April 2020 in the College of Medicine, Umm Al-Qura University in collaboration with Al-Noor Specialist Hospital, Makkah, Saudi Arabia. Complete blood count (CBC), serum iron, and ferritin levels were measured. Anti-H. pylori antibody was detected using anti-H. pylori immunoglobulin G enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of H. pylori infection among IDA patients was 62%. There was a significant difference between female and male subjects with a positive H. pylori status (p=0.001). There was also a significant difference between females and males with a positive H. pylori infection according to red blood cell count, hematocrit, mean corpuscular volume, and mean cor-puscular hemoglobin (p=0.001). CONCLUSION: The current study shows an association between H. pylori infection and unexplained IDA with significant difference between postmenopausal Saudi females and males. This will lead to more effective treatment in IDA and the eradication of H. pylori, as well as the prevention of recurrence, which are necessary and may provide a significant reduction in the overall disease burden.

Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients.

The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with controversial results. Our aim was to evaluate the association of the serum levels of the AGEs and their receptor sRAGE with cardiovascular disease (CVD) and the cardiovascular risk factors among HD patients. There were 130 HD patients and 80 age and gender matched control subjects were involved; 31.5% of the HD group were diabetic, which was an underlying cause of renal impairment; 36.1% had CVD, which was comprising 44.7% of diabetics and 55.3% of non-diabetic patients. The AGEs and sRAGE were assessed by enzyme linked immunosorbent assay (ELISA). In addition, the lipid profile, glycemic indices, pre-dialysis renal function tests, and hemoglobin % (Hb) were evaluated. The results show that the circulating AGEs and sRAGE levels were significantly higher in the HD patients. Those with underlying diabetes displayed higher sRAGE levels, which were positively correlated with hyperglycemia, HbA1C, and total cholesterol (TC). The HD patients with an increased serum sRAGE exhibited more cardiovascular risk factors (hypercholesterolemia and anemia) with a high prevalence of CVD. Using a linear regression analysis, we found a significant association of sRAGE with CVD and TC among HD patients, regardless of whether associating diabetes was an underlying cause of renal impairment. Overall, the HD patients displayed significantly higher serum AGEs with a concomitant increase in the circulating sRAGE levels, mainly in the diabetic HD, which were significantly associated with the CVD (independent predictors) and CV risk factors (hypercholesterolemia), mainly sRAGEs, regardless of the underlying diabetes mellitus. This highlights the prognostic role of AGEs and sRAGE in HD patients regardless of underlying cause in order to predict the risk for CVD.

Effect of variable antidiabetic treatments strategy on oxidative stress markers in obese patients with T2DM.

AIM: To evaluate the effect of different anti-diabetic treatment strategy on oxidative stress markers in patients with type 2 diabetes mellitus (T2DM). SUBJECT AND METHODS: A total of 93 patients with T2DM treated with metformin (G1 = 25), OHA (G2 = 22), OA and insulin (G3 = 26) and insulin alone (G4 = 20). In all patients, lipid profile and glycemic indices were assessed using routine laboratory tests. MDA and Oxidized LDL were assessed using commercially available ELISA kits. Laboratory tests were performed at baseline and at a control visit after 24 weeks of treatment. RESULTS: A significant decrease in the levels of MDA with improvement of glycemic control was observed in the group receiving OHA in combination with insulin therapy. A similar decrease of oxLDL was observed in all diabetic subgroups with borderline significance in those receiving metformin alone. The remaining clinical and biochemical parameters were not changed during follow-up in any of the involved groups. CONCLUSION: A combination therapy with insulin was more effective in glycemic control and MDA reduction in T2DM. Whereas, a significant oxLDLc reduction was observed in T2DM irrespective of categories of antidiabetic treatment or glycemic control.

Association of endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications.

This study evaluated the association of NOS3 polymorphisms with hypertension risk and complications. eNOS (G894T) SNP was performed by RT-PCR on 70 hypertensive patients (25 were hypertensive, 25 were hypertensive with CAD, and 20 were diabetic with hypertension) and 30 age- and gender-matched individuals. Lipid and glucose profile were assessed by standard colorimetric assay. Our results revealed that combination of (GT + TT) genotype and T allele significantly increases the risk of hypertension (OR = 3.86 and 4.33), respectively. Subgroup analysis showed significant association between CAD with eNOS (G894T) mutant genotype (P = 0.002) and allele frequency (P < 0.001). Moreover, the mutant homozygous and heterozygous eNOS genotype together were significantly associated with higher TC, LDLc, (P < 0.001), and TG (P = 0.001). Thus, hypercholesterolemia (P < 0.001 and OR = 12.48) increases the risk of hypertension among T carrier. These results indicated that the T carriers significantly increase hypertension risk and complication (CAD), mainly with hypercholesterolemia and in elderly.