Genome-wide association study for systemic lupus erythematosus in an egyptian population.

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

Establishment of reference intervals of clinical chemistry analytes for the adult population in Egypt.

BACKGROUND: This is the first Egyptian nationwide study for derivation of reference intervals (RIs) for 34 major chemistry analytes. It was conducted as a part of the global initiative by the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) for establishing country-specific RIs based on a harmonized protocol. METHODS: 691 apparently healthy volunteers aged ≥18 years were recruited from multiple regions in Egypt. Serum specimens were analyzed in two centers. The harmonization and standardization of test results were achieved by measuring value-assigned serum panel provided by C-RIDL. The RIs were calculated by parametric method. Sources of variation of reference values (RVs) were evaluated by multiple regression analysis. The need for partitioning by sex, age, and region was judged primarily by standard deviation ratio (SDR). RESULTS: Gender-specific RIs were required for six analytes including total bilirubin (TBil), aspartate and alanine aminotransferase (AST, ALT). Seven analytes required age-partitioning including glucose and low-density lipoprotein cholesterol (LDL-C). Regional differences were observed between northern and southern Egypt for direct bilirubin, glucose, and high-density-lipoprotein cholesterol (HDL-C) with all their RVs lower in southern Egypt. Compared with other collaborating countries, the features of Egyptian RVs were lower HDL-C and TBil and higher TG and C-reactive protein. In addition, BMI showed weak association with most of nutritional markers. These features were shared with two other Middle Eastern countries: Saudi Arabia and Turkey. CONCLUSION: The standardized RIs established by this study can be used as common Egyptian RI, except for a few analytes that showed regional differences. Despite high prevalence of obesity among Egyptians, their RVs of nutritional markers are less sensitive to increased BMI, compared to other collaborating countries.

Altered Functional Expression of ß-Adrenergic Receptors in Rhesus Monkey Embryonic Stem Cell-Derived Cardiomyocytes.

Pluripotent stem cells have demonstrated the potential to generate large numbers of functional cardiomyocytes (CMs) from different cell sources. Besides Wnt signaling, additional pathways are involved in early cardiac development and function. To date however, no study exists showing the effects of perturbing the canonical Wnt pathway using nonhuman primate embryonic stem (ES) cells. In this study, we investigated the effect of canonical Wnt inhibition during differentiation of nonhuman primate ES cell-derived CMs under defined, growth factor conditions. Rhesus monkey ES (rES) cells were differentiated into spontaneously beating CMs in the absence (control) or presence (treated) of Wnt inhibitor Dickkopf1 (DKK1), vascular endothelial growth factor, and basic fibroblast growth factor combined or added in a sequential manner during differentiation. Quantification and functional characterization of CMs were assessed by molecular and electrophysiological techniques. Analysis revealed no difference in average ratio of spontaneously beating clusters in both control and treated groups. However, the percentage of CMs was significantly reduced and the expressions of specific cardiac markers tested were also decreased in the treated group. Interestingly, we found that in CMs obtained from treated group, ß-adrenergic receptors (ß-ARs) were less expressed, their function was altered and electrophysiological studies revealed differences in action potential responsiveness to ß-AR stimulation. We demonstrated that the Wnt/ß-catenin pathway inhibitor, DKK1 associated with other growth factors repressed functional expression of ß-ARs in rES cell-derived CMs. Thus, control of this pathway in each cell line and source is important for proper basic research and further cell therapy applications.

Antibody screening in repeatedly transfused patients.

The purpose of pretransfusion compatibility testing is to prevent immune mediated hemolytic transfusion reactions. Our study aimed to evaluate the gel test for detection of clinically significant antibodies in repeatedly transfused patients. We investigated 200 thalassemic patients in whom, blood group, Rh-D, Rh phenotype determination, antibody screening and identification were done using an ID Microtyping System. Red cell alloantibodies were detected in 21 patients (10.5%). Among these patients, Anti-E was detected in 5 (23.8%), anti-D in 4 (19%), anti-K in 4 (19%), anti-e in 3 (14.3%) and each of anti-Fy(a), anti-Js(a), anti-Lu(a), anti-N and anti-s in one patient (4.8%). Anti-E showed the highest frequency in the 21 positive cases that developed clinically significant antibodies. The study revealed statistically significant correlation between development of transfusion reactions, frequency of blood transfusion and the duration of blood transfusion with the incidence of development of clinically significant alloantibodies. It is concluded that the gel test is an easy, quick and reliable method for detecting clinically significant antibodies. Antibody screening and identification is recommended prior to transfusion to detect if there is blood group incompatibility other than the ABO and Rh.