Salem Abbes

Publications (20) View all

• Article: The prevalence and prognostic significance of KRAS mutation in bladder cancer, chronic myeloid leukemia and colorectal cancer.

  Slah Ouerhani, Karim Bougatef, Ismail Soltani, Amel Ben Ammar Elgaaied, Salem Abbes, Samia Menif
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  ABSTRACT: Mutations in the KRAS gene have been shown to play a key role in the pathogenesis of a variety of human tumours. However the mutational spectrum of KRAS gene differs by organ site. In this study, we have analysed the mutational spectrum of KRAS exon 1 in bladder tumours, colorectal cancer (CRC) and chronic myeloid leukemia (CML). A total of 366 patients were included in the present study (234 bladder tumours, 48 CRC and 84 CML). The KRAS mutations are absent in BCR/ABL1 positive CML. This result suggests that BCR/ABL1 fusion gene and KRAS mutations were mutually exclusive. The frequency of KRAS mutations in bladder cancer was estimated at 4.27 %. All of mutations were found in codon 12 and 90 % of them were detected in advanced bladder tumours. However the correlation between KRAS mutations and tumour stage and grade does not report a statistical significant association. The KRAS mutations occur in 35.41 % of patients with CRC. The most frequent mutations were G12C, G12D and G13D. These mutations were significantly correlated with histological differentiation of CRC (p = 0.024). Although the high frequency of KRAS in CRC in comparison to bladder cancer, these two cancers appear to have the same mutational spectrum (p > 0.05).
  Molecular Biology Reports 05/2013; · 2.93 Impact Factor
• Article: Early complication in Sickle Cell Anemia children due to A(TA) _n TAA polymorphism at the promoter of UGT1A1 gene.

  Leila Chaouch, Emna Talbi, Imen Moumni, Arij Ben Chaabene, Miniar Kalai, Dorra Chaouachi, Fethi Mallouli, Abderraouf Ghanem, Salem Abbes
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  ABSTRACT: AIM: To determine the implication of the polymorphism namely A(TA)nTAA of UGT1A1 in lithogenesis for the first time in Tunisia among sickle cell anemia (SCA) children patients. MATERIAL AND METHODS: Our study was performed in 2010 and it involved 76 subjects chosen as control group characterized with normal hemoglobin status and presence of cholelithiasis and 102 SCA pediatric patients among whom 52 have cholelithiasis. We analyzed the polymorphism A(TA) _{n} TAA at the UGT1A1 promoter and the relationships between the various A(TA) _{n} TAA genotypes and alleles and bilirubin levels and occurrence of cholelithiasis. RESULTS AND DISCUSSION: The repartition of genotypes found according to serum bilirubin level shows a significant association between genotypes carried variant (TA) _{7} and hyperbilirubinemia (p< 0.05). We demonstrated the association of two genotypes with gallstones formation among SCA children patients: (TA) _{7} /(TA) _{7} and (TA) _{7} /(TA) _{8} with p=8.1 × 10 ^{ - 8} and p=0.01 respectively. (TA) _{7} and (TA) _{8} allele variants act as a risk factor for early gallstones formation in SCA patients with p=5.8 × 10 ^{ -9} and p=0.01 respectively. As for the control group only the genotype (TA) _{7} /(TA) _{7} presented a risk factor for gallstones formation. CONCLUSION: The novelty of this report is that it is the first time that a similar study was made on the Tunisian children sickle cell population and that the results show a clear association of (TA) _{7} variant in early gallstones formation in Tunisian SCA children. Interestingly our findings highlighted the association of (TA) _{8} variant as well, which was not found in previous studies.
  Disease markers 04/2013; · 1.64 Impact Factor
• Article: Implication of genetic variation at the promoter and exon1 of UGT1A1 in occurrence of cholelithiasis in Tunisia.

  Leila Chaouch, Yossra Said, Imen Moumni, Imen Mahjoubi, Arij Ben Chaabene, Imen Darragi, Abderraouf Ghanem, Salem Abbes
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  ABSTRACT: Bilirubin is conjugated with glucoronic acid in the liver by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms at the promoter region or exon1 of UGT1A1 gene result in unconjugated hyperbilirubinemia and could be at the origin of gallstone formation. The purpose of this study is to determine whether polymorphisms in the promoter area and exon 1 of UGT1A1 can be considered as a risk factor for lithogenesis. Our study involved 76 patients with cholelithiasis as well as 141 unaffected subjects. For each subject an analysis of the bilirubin parameters was performed. We screened genetic variation in the promoter and exon1 UGT1A1 namely the A (TA) nTAA and the six following SNPs: 44T>G, 101C>A, 115C>G, 145C>T, 211G>A and 222 C>A by PCR/sequencing. Our findings show that subjects with (TA)(7) or (TA)(8) variant in their genotypes are associated with high bilirubin level. Furthermore, the comparison between patients and controls according to A(TA)nTAA variation demonstrated that (TA)(6)/(TA)(7) and (TA)(7)/(TA)(7) genotype and (TA)(7) and (TA)(8) alleles were significantly associated with an increased risk of gallstone diseases p=0.0017, p= 6.1 10(-6), p=1.5 10(-6) and p=0.025 respectively. However, polymorphisms in exon1 were normal in all studied subjects except for the 211G>A which appears to be associated with a protective effect p=7.910(-9); OR=0.03, CI95% (0.001-0.158).
  Annales de biologie clinique. 12/2012; 70(6):702-6.
• Article: Microsatellite and Single Nucleotide Polymorphisms in the β-Globin Locus Control Region-Hypersensitive Site 2: Specificity of Tunisian β(S) Chromosomes.

  Maha Ben Mustapha, Imen Moumni, Amine Zorai, Kaïs Douzi, Abderraouf Ghanem, Salem Abbes
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  ABSTRACT: The diversity of sickle cell disease severity is attributed to several cis acting factors, among them the single nucleotide polymorphisms (SNPs) and (AT) rich region in the β-locus control region (β-LCR). This contains five DNase I hypersensitive sites (HS) located 6 to 22 kb upstream to the ϵ gene. The most important of these is the HS2 (5' β-LCR-HS2), characterized by the presence of three different SNPs and a microsatellite region known to be in association with β(S) chromosomes in various populations. The aim of this study was to present the molecular investigation of the 5' β-LCR-HS2 site in normal and sickle cell disease individuals in order to determine if there is any correlation or specificity between these molecular markers, the β(S) Tunisian chromosomes and phenotypical expression of sickle cell disease. One hundred and twenty-four chromosomes from Tunisian individuals (49 β(S) carriers and 13 normal individuals) were screened by polymerase chain reaction (PCR) and sequencing for the polymorphic short tandem microsatellite repeats (AT)(X)N(12)(AT)(Y) and the three SNPs (rs7119428, rs9736333 and rs60240093) of the 5' β-LCR-HS2. Twelve configurations of the microsatellite motif were found with an ancestral configuration elaborated by ClustalW software. Normal and mutated alleles were observed at the homozygous and heterozygous states for the three SNPs. Correlation between microsatellites and SNPs suggests that mutant SNP alleles were mainly associated, in the homozygous sickle cell disease phenotype, with the (AT)(8)N(12)GT(AT)(7) configuration, whereas, normal SNP alleles were associated with the (AT)(X)N(12)(AT)(11) configurations in normal β(A) chromosomes. The correlation of these various configurations with Hb F expression was also investigated. The principal component analysis (PCA) showed the correlation between the homozygous sickle cell disease phenotype, mutated SNP alleles and the Benin microsatellite configuration (AT)(8)N(12)GT(AT)(7), which confirmed the specificity of this configuration to the β(S) chromosomes. In addition, the observed high level of Hb F (14.6%) could play a protective role against Hb S to justify the modulation of sickle cell disease severity within the Benin haplotype compared to the other haplotypes. This study highlights the fact that the β-LCR-HS2 could be a genetic marker to identify the ethnic Tunisian β(S) chromosomes and facilitate the molecular diagnosis of sickle cell disease.
  Hemoglobin 10/2012; · 1.30 Impact Factor
• Article: Genetic polymorphisms of NQO1, CYP1A1 and TPMT and susceptibility to acute lymphoblastic leukemia in a Tunisian population.

  Slah Ouerhani, Nouha Cherif, Ikbel Bahri, Ines Safra, Samia Menif, Salem Abbes
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  ABSTRACT: Acute lymphoblastic leukemia (ALL) is the major pediatric cancer in developed countries. The etiology of ALL remains poorly understood, with few established environmental risk factors. These risks were influenced by co-inheritance of multiple low-risk genetic polymorphisms such as variants within cytochrome P450A1 (CYP1A1), NADPH: quinone oxidoreductase (NQO1) and Thiopurine methyltransferase (TPMT) genes. In this work, we conduct a case-control study to assess the impact of CYP1A1*2A (CYP1A1 T6235C); NQO1*2 (NQO1 C609T); TPMT*2 (TPMT G238C) and TPMT A719G polymorphisms on the risk of developing ALL. The frequencies of TPMT*2, TPMT A719G, NQO1*2 and CYP1A1*2 variants were examined in 100 patients with ALL and 106 healthy controls by allele specific PCR and/or PCR-RFLP methods using blood samples. We have found that NQO1 609CT genotype was overrepresented in patients and was associated with an aggravating effect compared to the reference group with NQO1 609CC genotype (p = 0.028, OR = 1.41; CI 95 %: 1.04-1.93). However, TPMT*2, TPMT 719*G and CYP1A1*2 variants did not appear to influence ALL susceptibility (p > 0.05). Moreover we have not found a significant correlation between the studied variants and Bcr-Abl transcript. In conclusion we retain that leukemogenesis of ALL is associated with carcinogens metabolism and consequently related to environmental exposures.
  Molecular Biology Reports 10/2012; · 2.93 Impact Factor