Role of micro-RNAs 21, 124 and other novel biomarkers in distinguishing between group 1 WHO pulmonary hypertension and group 2, 3 WHO pulmonary hypertension.

BACKGROUND: Pulmonary hypertension "PH" is considered a serious cardiovascular disease. World Health Organization divided PH into groups depending on many factors like pathological, hemodynamic, and clinical pictures. Lately, various micro-RNAs "miRNAs" and other novel biomarkers like endoglin and asymmetric dimethylarginine "ADMA" might have a role in diagnosis of PH and may differentiate between pulmonary arterial hypertension "PAH" and non-PAH. The purpose of the study is to show the role of miR-21, miR-124, endoglin and ADMA in the diagnosis of PH and distinguishing between WHO group 1 PH and WHO group 2 and 3 PH and to identify patients who might benefit from non-invasive and inexpensive tools to diagnose PAH. RESULTS: miR-21 was upregulated in group 1 PH, and there was significant difference between group 1 PH as compared with group 2 PH, group 3 PH and control; miR-124 was down-regulated in group 1 PH with highly significant difference between group 1 and group 2 PH and control but no significant difference with group 3 PH, endoglin was elevated in group 1 PH with a significant difference as compared to group 2 PH, group 3 PH and control. ADMA was elevated in group 1 PH as compared to control; however, there was no significant difference between it and group 2, 3 PH. CONCLUSIONS: miR-21, miR-124, endoglin and ADMA are good biomarkers to diagnose PH; however, only miR-21 and endoglin could distinguish group 1 PH from group 2 and 3 PH.

Current and novel modalities for management of chronic hepatitis B infection.

Over 296 million people are estimated to have chronic hepatitis B viral infection (CHB), and it poses unique challenges for elimination. CHB is the result of hepatitis B virus (HBV)-specific immune tolerance and the presence of covalently closed circular DNA as mini chromosome inside the nucleus and the integrated HBV. Serum hepatitis B core-related antigen is the best surrogate marker for intrahepatic covalently closed circular DNA. Functional HBV "cure" is the durable loss of hepatitis B surface antigen (HBsAg), with or without HBsAg seroconversion and undetectable serum HBV DNA after completing a course of treatment. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon. With these therapies, functional cure can be achieved in < 10% of CHB patients. Any variation to HBV or the host immune system that disrupts the interaction between them can lead to reactivation of HBV. Novel therapies may allow efficient control of CHB. They include direct acting antivirals and immunomodulators. Reduction of the viral antigen load is a crucial factor for success of immune-based therapies. Immunomodulatory therapy may lead to modulation of the host immune system. It may enhance/restore innate immunity against HBV (as toll-like-receptors and cytosolic retinoic acid inducible gene I agonist). Others may induce adaptive immunity as checkpoint inhibitors, therapeutic HBV vaccines including protein (HBsAg/preS and hepatitis B core antigen), monoclonal or bispecific antibodies and genetically engineered T cells to generate chimeric antigen receptor-T or T-cell receptor-T cells and HBV-specific T cells to restore T cell function to efficiently clear HBV. Combined therapy may successfully overcome immune tolerance and lead to HBV control and cure. Immunotherapeutic approaches carry the risk of overshooting immune responses causing uncontrolled liver damage. The safety of any new curative therapies should be measured in relation to the excellent safety of currently approved nucleos(t)ide analogues. Development of novel antiviral and immune modulatory therapies should be associated with new diagnostic assays used to evaluate the effectiveness or to predict response.

Impact of lifestyle modification on glycemic control and cognitive function among Type II diabetes mellitus patients.

Aim: Assessing impact of lifestyle modification on Type 2 diabetes mellitus (T2DM) glycemic control and cognitive function. Subjects & methods: Prospective study was conducted on T2DM patients (92 patients as interventional group and 92 patients conventional therapy). Results: After 6 months, significant improvements of HbA1c, oxidant and antioxidant, lipid profile, and cognitive function among only the interventional group (p < 0.05). Using logistic analysis, conventional therapy, DM duration >10 years, lower education, HbA1c baseline >7 were significant predictive risks for uncontrolled DM (AOR 4.2, 2.9, 2.7 and 2.2, respectively). While, conventional therapy, baseline mild cognitive impairment (MCI) and females were significant risks for MCI (AOR 11.5, 10.8 and 4.8, respectively). Conclusion: Lifestyle modification is a very important for glycemic control and cognitive function.Clinical Trial Registration: NCT04891887 (ClinicalTrials.gov).

The study aimed at assessing the effect of lifestyle modification program on Type 2 diabetes mellitus (T2DM) patients. The program contents include maintaining healthy diet depending on glycemic index and CHO counting, adjusting cholesterol level, regular physical activity for at least 30 minutes; 3­5 days per week, weight loss and maintaining an appropriate weight, controlling the blood pressure, smoking cessation and practicing mental activity. After 6 months, there was a significant improvement in glycemic control, cognitive function, oxidant and antioxidant and lipid profile levels among patients participating in the program but not among those remained on the conventional therapy.

Impact of direct-acting antiviral regimens on hepatic and extrahepatic manifestations of hepatitis C virus infection.

Hepatitis C virus (HCV) is a common cause of liver disease and is associated with various extrahepatic manifestations (EHMs). This mini-review outlines the currently available treatments for HCV infection and their prognostic effect on hepatic manifestations and EHMs. Direct-acting antiviral (DAA) regimens are considered pan-genotypic as they achieve a sustained virological response (SVR) > 85% after 12 wk through all the major HCV genotypes, with high percentages of SVR even in advanced fibrosis and cirrhosis. The risk factors for DAA failure include old males, cirrhosis, and the presence of resistance-associated substitutions (RAS) in the region targeted by the received DAAs. The effectiveness of DAA regimens is reduced in HCV genotype 3 with baseline RAS like A30K, Y93H, and P53del. Moreover, the European Association for the Study of the Liver recommended the identification of baseline RAS for HCV genotype 1a. The higher rate of hepatocellular carcinoma (HCC) after DAA therapy may be related to the fact that DAA regimens are offered to patients with advanced liver fibrosis and cirrhosis, where interferon was contraindicated to those patients. The change in the growth of pre-existing subclinical, undetectable HCC upon DAA treatment might be also a cause. Furthermore, after DAA therapy, the T cell-dependent immune response is much weaker upon HCV clearance, and the down-regulation of TNF-α or the elevated neutrophil to lymphocyte ratio might increase the risk of HCC. DAAs can result in reactivation of hepatitis B virus (HBV) in HCV co-infected patients. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, with clinical and immunological responses, and have rapid and high effectiveness in thrombocytopenia. DAAs improve insulin resistance in 90% of patients, increase glomerular filtration rate, and decrease proteinuria, hematuria and articular manifestations. HCV clearance by DAAs allows a significant improvement in atherosclerosis and metabolic and immunological conditions, with a reduction of major cardiovascular events. They also improve physical function, fatigue, cognitive impairment, and quality of life. Early therapeutic approach with DAAs is recommended as it cure many of the EHMs that are still in a reversible stage and can prevent others that can develop due to delayed treatment.

Multiple infections with hepatitis A virus and development of rheumatoid arthritis among waste water treatment plant workers.

INTRODUCTION: In the present work, we studied the association between multiple exposure of waste water treatment plant workers to infection with existing hepatitis A virus in waste water and development of rheumatoid arthritis, taking in consideration number of working years as an indicator for frequency of exposure to infection, compared to non waste water treatment plant workers. METHODOLOGY: A total of 105 waste water treatment plant workers and 48 NWWTPWs were included in the study. Exclusion criteria were positivity for HBV and/or HCV IgG, negativity to HAV IgG and suffering from rheumatic diseases other than rheumatoid arthritis. RESULTS: 96.2% of waste water treatment plant workers were anti-HAV-IgG positive, of whom 5 had high antibody titer indicating ongoing infection and were anti-HAV-IgM negative excluding primary infection. These 5 samples were further subjected to quantification of liver enzymes, glutamate oxaloacetate trasaminase and glutamate pyruvate transaminase and HAV-RT-PCR to check viremia and results showed increase of glutamate oxaloacetate trasaminase and glutamate pyruvate transaminase as well as viremea in all of them. Rheumatoid arthritis diagnosis was carried out by detection of C-reactive protein, rheumatoid factor and anti-cyclic citrullinated protein. Rheumatoid arthritis development was 19% in the waste water treatment plant workers with >10 working years and 8% for < 10 working years. Also, disease development started earlier (Age 30-40 years) among the waste water treatment plant workers compared to non waste water treatment plant workers (age: 40-50 years). CONCLUSIONS: Multiple exposures of waste water treatment plant workers to HAV might be one of the etiological stimuli of rheumatoid arthritis.

Correction: Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

[This corrects the article DOI: 10.1371/journal.pone.0236453.].

Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

OBJECTIVES: To assess the potential value of some miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI) among patients with type2 diabetes mellitus (T2DM) and to identify other risk factors for MCI among them. METHODS: This study enrolled 163 adults with T2DM using face to face interview. Cognitive function with its domains was assessed using Adenbrooke's Cognitive Examination III (ACE III). Lipid profile, glycated hemoglobin, and miR-128, miR-132, miR- 874, miR-134, miR-323, and miR-382 expressions, using quantitative real-time PCR, were assessed. RESULTS: MCI was detected among 59/163 (36.2%) patients with T2DM. Plasma expression of miR-132 was significantly higher in T2DM patients with MCI compared to those without MCI and to normal cognitive healthy individuals (median = 2, 1.1 and 1.2 respectively, P < 0.05. Logistic regression analysis showed that higher miR-132 expression with adjusted odds ratio (AOR): 1.2 (95% CI 1.0-1.3), female gender (AOR:2.1; 95%CI 1.0-4.3), education below postgraduate (secondary and university education with AOR: 9.5 & 19.4 respectively) were the significant predicting factors for MCI among T2DM patients. Using ROC curve, miR-132 was the only assayed miRNA that significantly differentiates T2DM patients with MCI from those with normal cognition with 72.3% sensitivity, 56.2% specificity, and 63.8% accuracy (P < 0.05). Other studied miRNAs showed lower sensitivity and specificity for detecting MCI among studied T2DM participants. CONCLUSION: MCI affects nearly one-third of adult patients with T2DM. A significantly over expression of miR-132 was detected among T2DM with MCI compared to those with normal cognition.

Association of anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes with HLA-DRB1 shared epitope alleles in Egyptian rheumatoid arthritis patients.

INTRODUCTION: The most common genetic risk factor for rheumatoid arthritis (RA) is human leucocyte antigen DRB1 (HLA-DRB1) shared epitope (SE). AIM: To investigate the relationship between anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), immunoglobulin (Ig)G, IgM and IgA and HLA-DRB1 SE among Egyptian patients with RA. METHODS: Serum levels of anti-CCP antibodies and RFIgG, RFIgM, RFIgA were assayed using enzyme-linked immunosorbent assay for 157 Egyptian RA patients and 150 healthy controls attending the outpatient clinics of National Research Center and Kasr El Aini Hospital. HLA-DRB1 genotyping was performed by the DynalAllSetTM polymerase chain reaction (PCR) single specific primer low-resolution typing kits. Amplified PCR product was checked using 3% agarose gel. RESULTS: HLA-DRB1-SE was found among 129 (82.2%) RA patients and 67 (44.7%) controls (odds ratio [OR] 5.7, CI 3.4-9.6, P < .0001). The risk of RA development was higher with the presence of SE two alleles (OR 11.6, P < .0001), while the OR for 1 copy SE allele was 4.4 (P < .0001). HLA-DRB1-SE was significantly associated with positive as well as negative anti-CCP and RF isotypes. The stronger association was with anti-CCP positivity with OR 11 (5.1-23.6), P < .0001. Furthermore, the risk of development of positive anti-CCP and RF isotypes was higher with the presence of 2 copies of SE alleles than with 1 copy. CONCLUSION: The prevalence of HLA-DRB1-SE is high in Egyptian RA patients. The role of SE in RA patients is most probably related to the development of anti-CCP positive RA rather than the development of anti-CCP positivity.

Risk Factors Associated with Mild Cognitive Impairment among Apparently Healthy People and the Role of MicroRNAs.

BACKGROUND: Mild cognitive impairment (MCI) is a stage between the expected cognitive decline of normal ageing and the serious decline of dementia. AIM: To identify risk factors and role of miRNAs associated with mild cognitive impairment (MCI) among employees. SUBJECTS AND METHOD: A cross-sectional study was carried out on 186 employees aged between 40 and 65 years. Cognitive function was evaluated using ACEIII, MoCA, and Quick cognitive tests. Medical history and lifestyle were assessed. Family 132 & 134 miRNA expressions were assessed by real-time PCR. RESULTS: MCI was detected among 14 / 186 (7.5%). miRNA 132 expression was the only significant miRNAs to detect MCI with low sensitivity and specificity (70%). The logistic analysis revealed that higher miRNA132 expressions, low monthly intake of; vegetables, unroasted nuts, low education and higher ALT levels were predicting factors for MCI with AOR 1.1 (1.01-3.3), 1.2 (1.04-1.43), 0.8 (0.8-0.98), 2.7 (1.9-7.4) and 1.6 (1.1-2.3) respectively. CONCLUSION: MiRNAs expression showed low sensitivity and specificity in detecting MCI; only miRNA 132 might be used. Several modifiable factors seem to reduce the risk of MCI.

CD33+ HLA-DR- Myeloid-Derived Suppressor Cells Are Increased in Frequency in the Peripheral Blood of Type1 Diabetes Patients with Predominance of CD14+ Subset.

INTRODUCTION: Type 1 Diabetes Mellitus (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas by autoreactive T cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that can potently suppress T cell responses. AIM: To detect the presence of MDSCs in T1D and compare their percentage in T1D versus healthy individuals. METHOD: Thirty T1D patients were included in the study. Diabetic patients with nephropathy (n = 18) and diabetic patients without nephropathy (n = 12). A control group of healthy individuals (n = 30) were also included. CD33+ and HLA-DR- markers were used to identify MDSCs by flow cytometry. CD14 positive and negative MDSCs subsets were also identified. RESULTS: MDSCs was significantly increased in T1D than the control group and diabetic patient with nephropathy compared to diabetic patients without nephropathy. M-MDSCs (CD14+ CD33+ HLA-DR-) were the most abundant MDSCs subpopulation in all groups, however their percentage decrease in T1D than the control group. CONCLUSION: MDSCs are increased in the peripheral blood of T1D with a predominance of the CD14+ MDSCs subset. Future studies are needed to test the immune suppression function of MDSCs in T1D.

Increased level of B cell differentiation factor in systemic lupus erythematosus patients.

Most autoimmune disease are driven by a dysfunction in T and B cells, but B cells are still an interesting area of research, perturbations in their development are implicated in autoimmune diseases. B cell differentiating factor (BCDF) plays a part in the differentiation of B cells. The aim was To assess the levels of BCDF, IgM and IgG in SLE patients and whether they have any peculiarity in the clinical context of SLE. Thirty six patients with SLE and 24 healthy volunteers as control were enrolled in the study. BCDF was measured using Sandwich ELISA, total human IgM and IgG were measured by calorimetric methods. The mean concentrations of BCDF and IgM were significantly higher in patients with SLE as compared with controls (P < 0.001 and P < 0.0001 respectively). No significant difference was observed as regard IgG. We observed positive correlation between BCDF and IgM (r = 0.281, P = 0.03), and between IgG and IgM, duration of the disease (r = 0.468, P = 0.004, r = 0.337, P = 0.008 respectively). Moreover we observed lower IgM level in patients with discoid lesion (P = 0.009) and lower IgG level in those with hematologic manifestations (P = 0.02). ROC analysis revealed area under curve (AUC) 0.861 for BCDF and 0.902 for IgM, they can delineate SLE from controls at a cut-off value of 98.5 pg/ml, and 18 mg/dl IgM respectively. CONCLUSION: BCDF and IgM are increased in SLE patients and are promissing diagnostic markers for SLE.

Expression of JAZF1, ABCC8, KCNJ11and Notch2 genes and vitamin D receptor polymorphisms in type 2 diabetes, and their association with microvascular complications.

BACKGROUND: We studied JAZF1, ABCC8, KCNJ11and Notch2 gene expression and vitamin D receptor (VDR) polymorphisms (Fok1 and Bsm1) in patients with type 2 diabetes mellitus (T2DM) and tried to find out their association with microvascular complications in these patients. METHODS: The study was conducted on 180 patients (93 complicated and 87 noncomplicated) and 150 healthy subjects. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to assess gene expression and real-time PCR was used to detect VDR genotypes. Serum vitamin D was assessed using Elisa technique. RESULTS: After adjustment for age, sex, body mass index and glycated hemoglobin, altered Notch2 gene expression was found between patients and controls and between complicated and noncomplicated cases (p = 0.001 and 0.001, respectively) and ABCC8 gene expression showed significant difference between patients and controls only (p = 0.003), while JAZF1and KCNJ11 expression showed no significant difference between the studied groups (p = 0.3 and 0.4, respectively). Serum vitamin D level was decreased in patients compared with controls (p = 0.001), while no difference was detected between complicated and noncomplicated cases (p = 0.1). Our results revealed no significant difference in VDR Fok1 and Bsm1 genotype distributions (p = 0.7 and 0.1, respectively) and allele frequencies (p = 0.4 and 0.1, respectively) between patients and controls. Patients with complications showed increased frequencies of Fok1GG genotype and G allele, while patients without complications showed increased frequencies of AA, then AG Fok1 genotype and A allele (p = 0.001 and 0.001, respectively). In addition, the frequencies of CC Bsm1 genotype and C allele were significantly higher among patients with complications, while frequencies of TT Bsm1 genotype and T allele were significantly higher among patients without complications (p = 0.02 and 0.003, respectively). CONCLUSION: Altered expression of Notch2 and ABCC8 genes may play a role in the pathogenesis of T2DM. Altered expression of Notch2 and VDR polymorphisms may play a role in the development of microvascular complications in diabetic patients. These results may assist in early identification and management of diabetic complications.

Association of STAT4 rs7574865 and PTPN22 rs2476601 polymorphisms with rheumatoid arthritis and non-systemically reacting antibodies in Egyptian patients.

The aim of this study was to investigate association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid arthritis (RA) susceptibility and to assess potential association with the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and neopterin were assayed in serum of 100 unrelated RA patients and 114 controls. STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the TaqMan allelic discrimination method. The frequency of STAT4 variant allele was significantly higher in RA patients than in controls (p = 0.01), while the variant allele of PTPN22 was identified in only two RA patients, in a heterozygous form and in none of control subjects. The frequency of STAT4 variant allele carrier genotypes (GT+TT) was significantly higher among RA patients than in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and dominant models. The frequency of RF and anti-CCP positivity was significantly higher among RA patients carrying T allele genotypes compared to patients carrying wild genotype (P = 0.02 and 0.04, respectively). No significant associations between STAT4 variant and serum neopterin or disease activity parameters were identified. Our study confirmed the association of STAT4 rs7574865 polymorphism with RA and was the first to indicate an association with RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role in susceptibility to RA in Egyptian patients.

Precision Phenotyping in Heart Failure and Pattern Clustering of Ultrasound Data for the Assessment of Diastolic Dysfunction.

OBJECTIVES: The aim of this study was to investigate whether cluster analysis of left atrial and left ventricular (LV) mechanical deformation parameters provide sufficient information for Doppler-independent assessment of LV diastolic function. BACKGROUND: Medical imaging produces substantial phenotyping data, and superior computational analyses could allow automated classification of repetitive patterns into patient groups with similar behavior. METHODS: The authors performed a cluster analysis and developed a model of LV diastolic function from an initial exploratory cohort of 130 patients that was subsequently tested in a prospective cohort of 44 patients undergoing cardiac catheterization. Patients in both study groups had standard echocardiographic examination with Doppler-derived assessment of diastolic function. Both the left ventricle and the left atrium were tracked simultaneously using speckle-tracking echocardiography (STE) for measuring simultaneous changes in left atrial and ventricular volumes, volume rates, longitudinal strains, and strain rates. Patients in the validation group also underwent invasive measurements of pulmonary capillary wedge pressure and LV end diastolic pressure immediately after echocardiography. The similarity between STE and conventional 2-dimensional and Doppler methods of diastolic function was investigated in both the exploratory and validation cohorts. RESULTS: STE demonstrated strong correlations with the conventional indices and independently clustered the patients into 3 groups with conventional measurements verifying increasing severity of diastolic dysfunction and LV filling pressures. A multivariable linear regression model also allowed estimation of E/e' and pulmonary capillary wedge pressure by STE in the validation cohort. CONCLUSIONS: Tracking deformation of the left-sided cardiac chambers from routine cardiac ultrasound images provides accurate information for Doppler-independent phenotypic characterization of LV diastolic function and noninvasive assessment of LV filling pressures.

Endothelial nitric oxide synthase gene (T786C and G894T) polymorphisms in Egyptian patients with type 2 diabetes.

BACKGROUND: Genetic factors play important role in the development of type 2 diabetes and diabetic nephropathy. Endothelial nitric oxide synthase (eNOS) gene is responsible for the bioavailability of nitric oxide and endothelial function. AIM: To assess the association of the endothelial nitric oxide synthase (eNOS) (T786C and G894T) single nucleotide polymorphisms with Egyptian type 2 diabetes mellitus and diabetic nephropathy. PATIENTS AND METHODS: A total of 200 type 2 diabetic patients and 100 apparently healthy volunteers as controls were included in the study. They were subjected to clinical examination and laboratory tests: fasting blood glucose, HBA1C, lipid profile, serum creatinine, blood urea and albumin creatinine ratio (ACR). Assessment of the T786C and G894T polymorphisms in the eNOS gene was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was no significant difference in distribution of eNOS T-786C polymorphism between patients and controls; TT genotype of eNOS G894T was more frequent in diabetic patients with and without albuminuria compared to controls. Patients were divided into 3 groups according to ACR. Normoalbuminuria: 37 patients with ACR ≤ 30 mg/g, microalbuminuria: 96 patients with ACR > 30 mg/g and ≤ 300 mg/g, and macroalbuminuria: 67 patients with ACR > 300 mg/g. There was no significant difference in genotype distribution of eNOS T-786C between the 3 groups of diabetic patients. The prevalence of TT genotype of eNOS G894T was higher in microalbuminuria patients compared to other groups. CONCLUSION: eNOS G894T variant may increase risk of type 2 diabetes with lack of association between eNOS T786C, eNOS G894T and DN in Egyptians.

Assessment of the -174G/C (rs1800795) and -572G/C (rs1800796) Interleukin 6 Gene Polymorphisms in Egyptian Patients with Rheumatoid Arthritis.

AIM: This study aimed to investigate genotype and allele frequencies of -174 (rs1800795) and -572 (rs1800796) IL-6 promoter gene polymorphisms in Egyptian patients with rheumatoid arthritis (RA) in comparison to control group. METHODS: The study was conducted on 198 Egyptian subjects (99 RA patients and 99 healthy control). The promoter region of the IL-6 gene was amplified by PCR using DNAs from patients and the controls, and their PCR products were digested by suitable enzymes. RESULTS: No statistical differences were found in -572G/C genotype (P = 0.177) or allele (P = 0.147) frequencies between RA patients and controls. Significant differences were observed in -174G/C genotype (P < 0.001) and allele (P < 0.001) frequencies between RA patients and controls. CONCLUSION: A significant association of IL-6 -174G/C gene polymorphism and RA in Egyptian population was found with significantly higher frequencies of GC and CC genotypes and C allele in RA patients compared to controls. No association was found between IL-6 -572G/C gene polymorphism and RA.

Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis.

To assess impact of PTPN22 1858C→T polymorphism, HLA shared epitope and autoantibodies on susceptibility and severity of rheumatoid arthritis (RA). A total of 150 RA patients and 150 controls were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor isotypes (IgG, IgM and IgA) were assayed by ELISA. PTPN22 1858C→T polymorphism was performed by RFLP analysis and HLA-DRB1 genotyping by PCR-SSP analysis. Single-view, anteroposterior radiographs of the hands and feet were obtained on all RA patients. The results showed association of PTPN22 1858 T allele with RA (OR = 2.3, 95 % CI 1.5-3.5) and bone erosion (OR = 2.9, 95 % CI 1.1-7.6). The associations increased with the combination of positive autoantibodies, HLA-DRB1 SE with PTPN22 1858 T allele carriage. The highest association was with the combination with anti-CCP antibodies (OR = 47.3, 95 % CI 10.9-204.4 for RA and OR = 69.4, 95 % CI 15.8-305.5 for erosion p < 0.001). Combination of PTPN22 1858 T allele carriage with negative RF isotypes or with absence HLA-DRB1 SE showed no significant association with RA. The presence of PTPN22 1858C→T polymorphism with HLA SE and autoantibodies increases risk of RA development and erosive disease.

Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Lipoprotein-related mechanisms have been associated with damage to the cardiovascular system in diabetic patients. Apolipoprotein E gene which affects the clearance of lipoproteins and consequently the lipid profile in our body is one of the most studied candidate genes and recently has been reported to be associated with T2DM and CAD. In this work, we studied the association of apoE gene polymorphism with T2DM and CVD and its effect on plasma lipids profile. METHODS: Our study was conducted on 284 subjects categorized into 100 patients with T2DM, 100 patients with T2DM complicated with CVD and 84 normal control subjects. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan(®) SNP Genotyping Assay. RESULTS: ApoE E3/E3 genotype was the most common in our subjects. The frequencies of E3/E4 genotype and ε4 allele were increased in both T2DM patients and CVD patients as compared with controls, but were significant only in CVD patients (p = 0.004 and 0.007, respectively). Diabetic patients who carried E3/E4 genotype were at 2.4-fold increased risk to develop CVD (95 % CI 1.14-5.19, P = 0.02) and the ε4 allele associated with 2.23-fold higher CVD risk (95 % CI 1.09-4.59, P = 0.02). After adjustment for other established risk factors, E3/E4 genotype was an independent risk factor for CVD (OR = 2.3, p = 0.009) but not for T2DM (OR = 1.7, p = 0.28), while ε4 allele was an independent risk factor for both T2DM (OR = 2.2, p = 0.04) and CVD (OR = 3.0, p = 0.018) with 5.9-fold increased risk to develop CVD in T2DM patients (p = 0.019). E3/E4 genotype associated with significantly higher levels of TC and non HDL-C in all groups and with significantly higher levels of LDL-C in both T2DM and CVD patients. CONCLUSIONS: ApoE gene polymorphisms associate with CVD and affect the lipid profile. The ε4 allele is an independent risk factor for both T2DM and CVD. Further genetic studies to add information beyond the traditional cardiovascular risk factors in T2DM and to identify risk genotypes will help in early prediction and identification of at risk patients.

Radius of proximal isovelocity surface area in the assessment of rheumatic mitral stenosis: Connecting flow to anatomy and hemodynamics.

BACKGROUND: Echocardiographic assessment of left atrial pressure (LAP) in mitral stenosis (MS) is controversial. We sought to examine the role of the radius of the proximal isovelocity surface area (PISA-r) in the assessment of the hemodynamic status of MS after fixing the aliasing velocity (Val). METHODS AND RESULTS: We studied 42 candidates of balloon mitral valvuloplasty (BMV), for whom pre-BMV echocardiography was done and LAP invasively measured before dilatation. PISA-r was calculated after fixing aliasing velocity to 33 cm/s. In addition, the ratio IVRT/Te'-E was also measured, where IVRT was isovolumic relaxation time, and Te'-E was the time difference between the onset of mitral flow E-wave and mitral annular early diastolic velocity. IVRT/Te'-E and PISA-r showed a strong correlation with LAP (r = -0.715 and -0.637, all p < 0.001) and with right-sided pressures. In addition, PISA-r correlated with mitral valve area by planimetry method (MVA) and with left ventricular outflow tract stroke volume (r = 0.66 and 0.71, all p < 0.001). Receiver operator characteristic curve (ROC-curve) showed that PISA-r was not inferior to IVRT/Te'-E in differentiating LAP ⩾25 from <25 mmHg. CONCLUSION: Provided that Val is set to a constant of 33 cm/s, PISA-r can assess the hemodynamic status of MS, and seems a simple alternative to the tedious IVRT/Te'-E for estimation of LAP.