👤 Raghda Saad Zaghloul Taleb

Osteoporosis (OP) is the most prevalent metabolic bone disease. Numerous genetic loci are strongly related to OP. AXIN1 is a significant gene that serves an important role in the WNT signaling pathway. The aim of this study was to explore the association between the AXIN1 genetic polymorphism (rs9921222) and OP susceptibility. A total of 101 subjects were enrolled in the study (50 patients with OP and 51 healthy individuals). Genomic DNA was extracted from whole blood using the QIAamp DNA Blood Mini Kit, and the AXIN1 gene polymorphism (rs9921222) was genotyped by TaqMan allelic discrimination assays. A logistic regression analysis was used to assess the association between genotypes and OP risk. We found that AXIN1 rs9921222 had a significant association with the susceptibility of OP under the homozygote model (TT vs. CC: OR = 16.6, CI = 2.03-136.4, p = 0.009), (CT vs. CC: OR = 6.3, CI = 1.23-31.8, p = 0.027), recessive genetic model (TT vs.TC-CC: OR = 13.6, CI = 1.7-110.4, p = 0.015), and the dominant model (TT-TC vs. CC: OR = 9.7, CI = 2.6-36.3, p < 0.001). Allele T was significantly associated with OP risk (T vs. C: OR = 10.5, CI = 3.5-31.15, p = 0.001). There was a statistically significant difference between genotypes in mean platelet volume (p = 0.004), and platelet distribution width (p = 0.025). In addition, lumbar spine bone density, and femur neck bone density were significantly different between genotypes (p < 0.001). AXIN1 rs9921222 was associated with OP susceptibility in the Egyptian population and should be considered a potential determinant risk for OP. Show less

Notch signaling is an important cellular pathway which affects the development and function of many organs. It plays critical roles in maintaining of progenitor stem cell population as well as balancing cell proliferation, survival, differentiation and apoptosis. It has been shown that notch signaling is aberrantly activated during the carcinogenesis of a variety of human cancers. In this study we aimed to explore activation of this signaling pathway in esophageal squamous cell carcinoma (ESCC) through expressional analysis of notch signaling target genes. The mRNA expression of HEY1 and HEY2 was comparatively analyzed by real-time PCR in tumor and related margin normal tissues of 50 ESCC patients. Comparative quantitative real-time PCR indicates the overexpression of HEY1 and HEY2 in 54 and 30% of ESCC samples, respectively. Overexpression of HEY1 was significantly associated with stage of the tumor (p = 0.048) and tumor location (p = 0.008). HEY2 overexpression was also significantly correlated to node metastasis of tumor cells (p = 0.043). Overexpression of HEY1 and HEY2 in ESCC is correlated to different indices of poor prognosis and it is extrapolated that such overexpression is important in progression and development of ESCC tumorigenesis. To the best of our knowledge, this is the first report introducing aberrant activation of notch signaling target genes in ESCC, where it plays roles in development and progression of the malignancy and may be considered in therapeutic modalities to restrict ESCC progression. Show less

Lysosomal storage disorders (LSD) are rare entities of recessive inheritance. The presence of a "founder" mutation in isolated communities with a high degree of consanguinity (e.g., tribes in the Middle East North Africa, MENA, region) is expected to lead to unusually high disease prevalence. The primary aim of this study was to estimate the prevalence of LSD and report their mutation spectrum in UAE. Between 1995 and 2010, 119 patients were diagnosed with LSD (65 Emiratis and 54 non-Emiratis). Genotyping was performed in 59 (50 %) patients (39 Emirati from 17 families and 20 non-Emiratis from 17 families). The prevalence of LSD in Emiratis was 26.9/100,000 live births. Sphingolipidoses were relatively common (9.8/100,000), with GM1-gangliosidosis being the most prevalent (4.7/100,000). Of the Mucopolysaccharidoses VI, IVA and IIIB were the predominant subtypes (5.5/100,000). Compared to Western countries, the prevalence of fucosidosis, Batten disease, and α-mannosidosis was 40-, sevenfold, and fourfold higher in UAE, respectively. The prevalence of Pompe disease (2.7/100,000) was similar to The Netherlands, but only the infantile subtype was found in UAE. Sixteen distinct LSD mutations were identified in 39 Emirati patients. Eight (50 %) mutations were reported only in Emirati, of which three were novel [c.1694G>T in the NAGLU gene, c.1336 C>T in the GLB1 gene, and homozygous deletions in the CLN3 gene]. Twenty-seven (42 %) patients were clustered in five of the 70 Emirati tribes. These findings highlight the need for tribal-based premarital testing and genetic counseling. Show less