👤 Sema Kandil

The lack of effectiveness of acute myeloid leukemia (AML) treatment remains a major challenge and resembles a principal cause of AML-related mortality owing to chemotherapy resistance. SNAI1 has been proved to be a leading factor in drug resistance in many cancer types. However, its relation to chemoresistance in AML is not well understood. In addition to standard lab work, the expression level of SNAI1 was determined in bone marrow samples of 109 adult and pediatric patients with de novo acute myeloid leukemia using RT-qPCR. The relation between SNAI1 and AML drug resistance and immunomodulatory genes was investigated using the STRING tool. The SNAI1 expression level was upregulated in AML patients in particular samples with promyelocytic leukemia subtype against control cases. In the treatment response, SNAI1 was significantly higher in resistant patients in comparison with the complete remission group. SNAI1 overexpression was associated with high initial blasts and total leukocyte counts, but with HLA class II histocompatibility antigen DR downregulation. STRING analysis showed that multiple drug resistance and immunomodulatory genes of AML induce SNAI upregulation and activation. Kaplan-Meier analysis indicated that there was no relation between SNAI1 expression level and patient survival status. We conclude that the SNAI1 expression level may be a predictor of intrinsic drug resistance incidence in AML patients. Show less

Genetic etiologies of autism spectrum disorders (ASD) are complex, and the genetic factors identified so far are very diverse. In complex genetic diseases such as ASD, de novo or inherited chromosomal abnormalities are valuable findings for researchers with respect to identifying the underlying genetic risk factors. With gene mapping studies on these chromosomal abnormalities, dozens of genes have been associated with ASD and other neurodevelopmental genetic diseases. In the present study, we aimed to idenitfy the causative genetic factors in patients with ASD who have an apparently balanced chromosomal translocation in their karyotypes. For mapping the broken genes as a result of chromosomal translocations, we performed whole genome DNA sequencing. Chromosomal breakpoints and large DNA copy number variations (CNV) were determined after genome alignment. Identified CNVs and single nucleotide variations (SNV) were evaluated with VCF-BED intersect and Gemini tools, respectively. A targeted resequencing approach was performed on the JMJD1C gene in all of the ASD cohorts (220 patients). For molecular modeling, we used a homology modeling approach via the SWISS-MODEL. We found that there was no contribution of the broken genes or regulator DNA sequences to ASD, whereas the SNVs on the JMJD1C, CNKSR2 and DDX11 genes were the most convincing genetic risk factors for underlying ASD phenotypes. Genetic etiologies of ASD should be analyzed comprehensively by taking into account of the all chromosomal structural abnormalities and de novo or inherited CNV/SNVs with all possible inheritance patterns. Show less

This study aimed to analyze the association between UBE2E2, G6PC2, PROX1, DUSP9, ADCY5 and APOC3 polymorphisms and the risk of metabolic syndrome (MetS) in Moroccan patients. The study was applied on 316 unrelated individuals from Morocco, 177 MetS patients and 139 controls. The metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) criteria. All subjects were genotyped for the following polymorphisms: rs7612463 (UBE2E2), rs560887 (G6PC2), rs340874 (PROX1), rs5945326 (DUSP9), rs11708067 (ADCY5) and rs5128 (APOC3) using TaqMan allelic discrimination assay and PCR-RFLP. The rs5128 (APOC3) and rs340874 (PROX1) polymorphisms were found to be significantly associated with susceptibility to MetS (P=0.003 and P=0.033, respectively), with odds ratios (ORs) of 4.39 (95% CI=1.66-11.56) and 2.81 (95% CI=1.09-7.27), respectively. Two variants presented a tendency to be protector factors against MetS risk: rs5945326 in DUSP9 gene (OR=0.32; 95% CI=0.17-0.62; =0.001) and rs11708067 in ADCY5 gene (OR=0.51; 95% CI=0.28-0.95; P=0.034). No association was detected between rs7612463 (UBE2E2) and rs560887 (G6PC2) SNPs and MetS increased risk. This study suggests a potential role of rs5128, rs340874, rs5945326 and rs11708067 variants in MetS susceptibility in the Moroccan population. Show less

The aim of the present study is to explore the association between the APOA5 polymorphisms and haplotypes with obesity in Moroccan patients. The study was performed in 459 subjects, Obese (n=164) and non-obese (n=295). All subjects were genotyped for the APOA5 -1131T>C (rs662799) and c.56C>G (rs3135506) polymorphisms. The contribution of APOA5 polymorphisms and haplotypes in the increased risk of obesity were explored using logistic regression analyses. The -1131T>C and c.56C>G polymorphisms were significantly associated with obesity. Both polymorphisms were strongly associated with increased BMI. Analysis of constructed haplotypes showed a significant association between CG haplotype and susceptibility to obesity (OR [95%CI]=3.09 [1.93-4.97]; P<0.001). These results support a potential role for APOA5 common variants and related haplotypes as risk factors for obesity. Show less