West Algerian Population Research Articles

The Frequencies distribution of CYP3A5 rs776746 and ABCB1 rs1045642 polymorphisms in the west Algerian population and relationships with pharmacogenetics.

Pharmacogenetic markers, such as the ATP Binding Cassette (ABCB1) and cytochrome P450 (CYP) 3A5 enzymes, play a crucial role in personalized medicine by influencing drug efficacy and toxicity based on individuals' or populations' genetic variations.This study aims to investigate the genetic polymorphisms of CYP3A5 (rs776746) and ABCB1 (rs1045642) in the West Algerian population and compare the genotypes and allelic distributions with those of various ethnic groups. The study involved 472 unrelated healthy subjects from the Western Algerian population. DNA genotyping was performed using TaqMan allelic discrimination assay. The variants in our population were compared to those in other ethnic groups available in the 1000 Genomes Project. Genotype and allele frequencies were calculated using the chi-square test and the Hardy-Weinberg equilibrium (HWE). The minor allele frequencies were found to be 0.21 for CYP3A5 6986A and 0.34 for ABCB1 3435T. These frequencies were similar to those observed in North African populations, while notable differences were observed in comparison to certain Caucasian and African populations. The difference in the allelic and genotypic distribution of these polymorphisms emphasize the need for dose adjustments in drugs metabolized by CYP3A5 and transported by ABCB1 to optimize treatments outcomes.

Clinical profile of FTL3-ITD mutation in West Algerian population with acute myeloid leukemia.

Acute myeloid leukemia(AML) is a cancer of the myeloid line of blood cells, characterized by the abnormal and rapid growth of cells. The mutation of the Fms-like tyrosine kinase 3 ligand gene (FLT3-ITD) represents an important factor in the prognosis of AML. The objective of this study was to determine for the first time the prevalence of FLT3-ITD mutation in west Algerian AML patients. A total of 160 AML patients were genotyped for FLT3-ITD mutation by using polymerase chain reaction. FLT3-ITD mutation was detected in 13% of patients. Mutation rates show no significant difference in the distribution of sex and age. A positive association was found between this mutation and a higher leukocyte and blast cells counts. We also found that the M3 and M5 subtype were the commonest in the FLT3 mutated group. This preliminary study provides first-time prevalence estimates for FLT3-ITD mutation in acute myeloid leukemia patients from the West region of Algeria.

Epidemiological Study and Clinical Characteristics of Crohn's Disease in The West Algerian Population

Epidemiological Study and Clinical Characteristics of Crohn's Disease in The West Algerian Population

Pregabalin addiction caracteristics at oran: A cohort study

IntroductionPregabalin is an analogue of gamma-aminobutyric acid (GABA). Recent reports suggest illicit pregabalin use may be increasing among youth, however its addictive potential has not been well established (1).ObjectivesDrug seeking behavior and chronic drug use are associated with defcits in glutamate clearance and activation of postsynaptic glutamatergic receptors (2). Based upon multiple studies, we compare here the addiction and misuse risks of pregabalin with those of traditional psychoactive substances (3).MethodsUsers of pregabalin were identified from 1st January 2019 to 31 December 2019 in Oran Addictology service, at west Algeria. The aim of the study was to establish the addictive potential of pregabalin and to compare the addiction risks of pregabalin with traditional psychoactive substances in west Algerian population. Clinical diagnosis was established according DSM-5 diagnosis criteria.ResultsA total of 92 cases of pregabalin abuse or dependence were identified. The principal population at risk consists of patients with other current or past substance use disorders, for the most part opioid and multi-drug users, the age group were between 17-38 years old, mostly single men. The mean daily dose of pregabalin was 1200 mg. Almost all patients experienced withdrawal symptoms when pregabalin was discontinued.ConclusionsThe misuse of pregabalin often leads to abuse and dependence, mostly in the context of multiple drug addiction, especially in youth population.

Association study of copy number variants in CCL3L1, FCGR3A and FCGR3B genes with risk of ankylosing spondylitis in a West Algerian population.

Numerous single nucleotide polymorphisms (SNPs) were explored in the Algerian population to evaluate associated ankylosing spondylitis (AS) genetic risk factors, but no study has identified the impact of copy number variations (CNVs). The aim of the study was to determine whether CNVs of CCL3L1, FCGR3A and FCGR3B genes were also associated with the susceptibility of AS disease in Algerian population. The data set of the current study is composed of 81 patients with AS and 119 healthy controls. All samples were genotyped by digital droplet PCR (ddPCR). Chi-square test and OR calculation were used to evaluate association between CNVs and AS and the risk associated with copy numbers (CN). In results, FCGR3A CN less than two copies (<2) was significantly increased in spondylitis patients (p=.0001, OR=7.74 [2.32-25.74]). Additionally, FCGR3A CN<2 copies association was present only in HLA-B27 (-) patients. We have concluded that FCGR3A deletions have an independent effect on AS regarding HLA-B27 status. This is the first study that investigated the CCL3L1 CNVs in relation to AS risk disease. It reveals that CCL3L1 and FCGR3B CNVs may not be involved in susceptibility to AS risk in the Algerian population.

Association of the HLA-B27 antigen and the CTLA4 gene CT60/rs3087243 polymorphism with ankylosing spondylitis in Algerian population: A case-control study.

Ankylosing spondylitis (AS) is a complex inflammatory disease that represents a major health problem both in Algeria and worldwide. Several lines of evidence support that genetic risk factors play a role in AS etiology and the CTLA4 gene has attracted a considerable attention. In this study, we were interested in evaluating the HLA-B27 frequency and in exploring the CTLA4 gene in a sample of the North African population. The dataset of the current study is composed of 81 patients with AS and 123 healthy controls. All samples were genotyped by TaqMan® allelic discrimination assay. The genetic risk of the HLA-B27 specificity and the CTLA4/CT60 polymorphism were assessed by odds ratios (OR) with 95% confidence intervals (CI). High spondylitis risk was detected for HLA-B27 allele (OR= 14.62, p=10-6 ) in addition to a significant association of the CT60*G allele (OR= 1.89, p=.002). After gender and age stratifications, the association of the CT60*G allele was still significant in females sample (OR= 2.10, p=.001) and when age up to 30years (OR = 2.21, p=.008). Interestingly, the CT60*G allele revealed an increased spondylitis risk in the B27 negative group (OR= 2.81, p=.006). The present work showed in West Algerian population that the HLA-B27 antigen and the variation in the CTLA4 3'UTR region played an important role in the ankylosing spondylitis susceptibility. The heterogeneity of this disease is deduced by genetic difference found between B27+ and B27- groups.

Polymorphism rs3087243 is associated with the occurrence of ankylosing spondylitis in the West Algerian population

Background: Numerous studies have shown that polymorphism rs231775 of the CTLA4 gene is strongly implicated in the development of ankylosing spondylitis (AS). Other polymorphisms of this gene are candidates that may have an additional effect in susceptibility to AS. For the first time, we searched for the association of rs3087243 polymorphism located in the 3'UTR region of the CTLA4 gene with the development of SA in the Algerian population.&#x0D; Methods: The study involved 200 subjects (80 AS patients recruited at the rheumatology service and 120 healthy individuals unrelated). Genotyping was performed by real-time PCR (Taqman®). Analysis of the results was carried out by IBM.SPSS.Statictis® software.&#x0D; Results: The distribution of allele frequencies showed a significant association between the GG genotype of the polymorphism rs3087243 and AS risk (OR= 1.77 [0.98-3.21], p=0.004).&#x0D; Conclusion: Our data would suggest that the 3'UTR region of the CTLA4 gene could have an impact on the development of SA in the West Algerian population. These results need to be confirmed on a larger sample.

No correlation between MTHFR c.677 C > T, MTHFR c.1298 A > C, and ABCB1 c.3435 C > T polymorphisms and methotrexate therapeutic outcome of rheumatoid arthritis in West Algerian population.

The c.677 C > T and c.1298 A > C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene and c.3435 C > T polymorphism of ATP-Binding cassette B1 (ABCB1) gene are reported as pharmacogenetic markers, influencing the methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA) patients. The aims of this study were to determine the relationship between these polymorphisms and clinical response and/or adverse drug reaction (ADRs) to MTX treatment. The cohort of our study was composed of 110 RA patients of the West Algerian population. The clinical response was evaluated using the disease activity score 28 (DAS28) and the ADRs were collected after physical examination of patients. All samples were genotyped for theses polymorphisms by TaqMan® allelic discrimination assay. Based on EULAR criteria, 59.09% RA patients were responders and ADRs were observed in 40.9% patients. The frequency distribution of these three polymorphisms was similar between the responders and the non-responders. The same result was found on ADRs study and no significant difference of distribution between the presence of ADRs group and absence of ADRs group was observed. Our study joins the results that found in others population in the world. We have demonstrated, for the first time in the West Algerian population, that these polymorphisms were not predictive for clinical response and/or ADRs to MTX therapeutic outcome.

Effects of CYP3A5 and ABCB1 Genetics Variant on Tacrolimus Pharmacokinetics in Algerian adult Kidney Transplant Patients

Objective: The aim of this study is to determine the impact of CYP3A5 c. 6986A>G and ABCB1 c. 3435C>T polymorphisms on Tacrolimus (Tac) pharmacokinetics in Algerian kidney recipients transplant. Pharmacogenetics methods may be used prospectively to aid dose selection and individualize immunosuppressive therapy. Methods: Sixty three kidney transplant patients from West Algerian population were enrolled in the study. The Tac pharmacokinetic parameters were calculated from patients blood. The Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and data were analyzed by χ2. Results: Our findings suggest that there is a significant distribution of TAC Concentration/Dose Ratio in Days 30 to 90 for these polymorphisms. However, at the sixth month after transplantation the Tac concentration/Dose Ratio present a significant distribution for only the CYP3A5 c. 6986A>G polymorphism. Conclusion: We have shown, for the first time in Algerian population that theses polymorphisms are not an important genetic factor on Tac pharmacokinetics. Keys Words: Kidney transplant, CYP3A5, ABCB1, Tacrolimus, cyclosporine, Algeria, polymorphism. www.jmscr.igmpublication.org Impact Factor 5.244 Index Copernicus Value: 5.88 ISSN (e)-2347-176x ISSN (p) 2455-0450 DOI: http://dx.doi.org/10.18535/jmscr/v4i4.34

P-191 Exploration of the implication of thymidylate synthase polymorphisms on the risk of colorectal cancer in west Algerian population

P-191 Exploration of the implication of thymidylate synthase polymorphisms on the risk of colorectal cancer in west Algerian population

No association between XRCC3 Thr241Met and XPD Lys751Gln polymorphisms and the risk of colorectal cancer in West Algerian population: a case–control study

Colorectal cancer (CRC) is a complex and multifactorial disease, in which genetic and environmental factors both seem to play a part. Many epidemiological studies have explored the association between genetic polymorphisms of X-ray repair cross-complementing group 3 (XRCC3) (Thr241Met) and Xeroderma pigmentosum group D (XPD) lysine to glutamine at codon 751 (Lys751Gln) and risk of CRC in various populations; however, the results are controversial. We conducted this case-control study in a West Algerian population to assess the potential role of this genetic polymorphism on the risk of CRC in this population. Genomic DNA was extracted from blood samples collected from 129 sporadic CRC patients and 148 normal controls. The polymorphisms were determined by pyrosequencing technique. The distribution of XRCC3 Thr241Met and XPD Lys751Gln genotypes among controls did not differ significantly from those predicted by the Hardy-Weinberg distribution (p > 0.05). There were no significant differences in the genotypes distribution and allele frequencies between CRC patients and controls. A significant association was found between the combined heterozygous of XRCC3 and homozygous variant of XPD gene and CRC. This is the first study on DNA repair genetic polymorphisms in West Algerian population, and it suggests that the XRCC3 Thr241Met and XPD Lys751Gln polymorphisms may not be associated with the CRC risk in this population.

Prevalence of JAK2 V617F mutation in west algerian population with chronic myeloproliferative neoplasms: A multicenter study

JAK2 V617F point mutation is now well recognized in patients with chronic myeloproliferative neoplasms (MPNs). However, its frequency in Algerian patients is still unknown. We determined the JAK2 V617F mutation in blood samples from 344 patients from five hematology departments across West Algeria, using amplification refractory mutation system-polymerase chain reaction (ARMSPCR). The JAK2 V617F mutation was identified in 157/344 patients (45.63%), 80/98 polycythemia vera patients (81.6%), 44/75 essential thrombocythemia patients (58.6%), 6/13 primary myelofibrosis patients (46.2%), 21/87 with suspected MPN (12.9%), and 2/32 secondary thrombocytosis patients (6.2%), but was not detected in 28 patients with secondary erythrocytosis. Detection of JAK2 V617F mutation is an essential molecular tool to establish myeloproliferative neoplasm diagnosis, which allowed us to adjust the diagnosis for 6 patients and should be systematically included into the initial evaluation of patients suspected of MPNs in Algeria.

O760 - The anthropological study of MHC in west Algerian population reveals intermediate genetic distances between Moroccans and Egyptians

O760 - The anthropological study of MHC in west Algerian population reveals intermediate genetic distances between Moroccans and Egyptians