Egyptian Journal of Biochemistry and Molecular Biology

Abstract association between genetic variants of single nucleotide polymorphisms of the Discoidin Domain Receptor Tyrosine Kinase 1 (DDR1) a/c (rs 2267641) and Granzyme B (GZMB) C/T (RS8192917) genes in vitiligo

Amany A. Saleh, Wafaa A. Shehata, Mohammed G. Elhelbawy, Nesreen G. Elhelbawy — Tue, 09 Feb 2021 00:00:00 +0000

Vitiligo manifests as advanced loss of melanocytes with reduced cellular adhesion. Discoidin Domain Receptor Tyrosine kinase1 (DDR1) is a main element affecting cellular adhesiveness associated with vitiligo. Granzyme B (GZMB) has significant role in cytotoxic T-cell induced apoptosis. This study aimed to evaluate the association between genetic variants of single nucleotide polymorphisms of DDR1 A/C (rs 2267641) and GZMB C/T (rs8192917) and the risk of developing vitiligo. The genotypes were investigated using allele discrimination assay comparing 120 patients having non-segmental vitiligo and 100 age and gender matched healthy individuals. We detected a significant prevalence of the CC genotype and C allele of both DDR1 and GZMB polymorphisms in vitiligo patients with early onset and progressive course compared to controls. Our results concluded that DDR1 A/C (rs 2267641) and GZMB C/T (rs8192917) polymorphisms may be risk factors for vitiligo.

The study of long non-coding RNAs(NAALADL2 and XIST) gene expression in diffuse large B cell lymphoma

Fatma M Mohammed, Rania A El Shazly, Suzy F Gohar, Shimaa E. Soliman — Tue, 09 Feb 2021 00:00:00 +0000

Diffuse large B cell lymphoma (DLBCL) is the most predominant type of Non Hodgkin- Lymphomas, representing more than one third of all recently diagnosed cases. Long non-coding RNAs (lncRNAs) are a class of RNA not coding for protein having more than 200 nucleotides and have significant roles in tumor formation and they have been investigated in different types of solid and hematologic tumors, including DLBCL.This work aims to study the level of lncRNAs(NAALADL2 and XIST)gene expression in DLBCL.NAALADL2 and XIST gene expression levels in blood were performed by real time qPCR technique. Forty five DLBCL patients and forty five age and gender matched healthy controls were included in this study.There was significant statistical increase in the expression of NAALADL2 and decrease of XIST expression in patients compared to control group (p value < 0.001). From this study, ROC curve analysis revealed cut-off values>10.3 and<1.57 for NAALADL2 and XISTrespectively.There was significant positive correlation between NAALADL2 and advanced stage and a significant negative correlation is found between XIST and advanced stage. It may be concluded that NAALADL2 and XISTexpression levels were obviously associated with DLBCL and might determine the disease progression.

CYP2D6 expression is cumulatively up regulated in multidrug treated hepatoma cells: a predective pharmacogenetics in vitro model

Sherine Khedr, Thoria Donia, Elsayed Ibrahim Salim, Mohamed Hessien — Tue, 09 Feb 2021 00:00:00 +0000

Cancer and many other diseases require concomitant treatments with combinations of many drugs.Debrisoquine 4-Hydroxylayase (CYP2D6) is microsomal enzyme involved in phase I metabolism of a long list of drugs. Also, it is a marker of inter-individual variability in drug responsiveness. This study was designated to explore the regulation of CYP2D6 in hepatoma cells exposed to combinations of anticancer and epigenetic modifying drugs. HepG2 cell were treated with combinations of anticancer drug (Taxol), glucocorticoid (dexamethasone, DEX) and epigenetic modifiers: Trichostatin A (TSA) and 5 aza-deoxycytidine (5 aza-dC). The expression of CYP2D6 was determined by quantitative RT-PCR and compared to other CYPs and the corresponding cumulative apoptotic effect was determined by flow cytometry. The obtained results revealed thatUnder non-induced conditions, CYP2D6 was stably expressed and sub micromolar concentration of DEX mildly increased its expression. Individual treatments as DEX, Taxol, TSA and 5-azadC induced 2-6-fold increase in the transcript level, where the TSA was the most potent inducer. Combinations of 2 drugs as (Taxol+DEX), (Taxol+TSA), (Taxol+5-aza-dC) and (TSA+5-aza-dC). led to 3-10-fold increase (average 6.2), whereas cocktails of 3 drugs as (Taxol+DEX+5-aza-dC), (Taxol+DEX+TSA) and (Taxol+TSA+5-aza-dC) led to further up regulatory effect (11-27-fold). The highest increment (28-fold) was observed when cells were treated with 4 drugs as (Taxol+TSA+5-aza-
dC+DEX). The progressive induction of CYP2D6 was correlated with the cumulative apoptotic effect (r=0.79). Conclusively, the data suggest, for the first time, that anticancer, epigenetic regulatory factors and dexamethasone cumulatively enhanced the baseline expression of CYP2D6.