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Background/Aim: To investigate the possible association between the polymorphism of the CTLA-4 exon 1 +49 A/G and susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population. Methods: The +49 A/G dimorphism was analyzed in 119 patients with CD, 65 patients with UC, and 100 controls by the polymerase chain reaction-restriction fragment length polymorphism method. Results: Significantly higher frequencies of the CTLA-4 +49A allele and A/A homozygous individuals were observed in patients with CD when compared with controls (pc = 0.0023 and pc = 0.0003, respectively). Analysis of CTLA-4 A/G polymorphism with respect to sex in CD showed a significant difference in A/A genotypes between female patients and controls (pc = 0.0001 and pc = 0.038, respectively). There were no differences in the subgroups of patients with CD. Conclusions: Forty-nine A alleles and AA genotype are associated with CD susceptibility in Tunisians. Other genes involved in the T-cell regulation remain strong candidates for IBD susceptibility and require further investigation. [ABSTRACT FROM AUTHOR]

Background: In this study, we evaluated the prevalence of the most common mutations occurring in Enhancer II (EnhII), Basal Core Promoter (BCP), Precore (PC), and Core (C) regions of hepatitis B virus (HBV) genome. Objectives: We also investigated the correlation between HBV variants, their genotypes, and patients' HBe antigen (HBeAg: soluble shape of the capsid antigen) status. Patients and Methods: We retrieved viral DNA from 40 serum samples of Tunisian patients positive for hepatitis B surface antigen (HBsAg) and HBV DNA, amplified the above mentioned regions using specific primers, and sequenced the corresponding PCR (polymerase chain reaction) products. For further analysis purpose, the patients were divided into two groups: Group1 including 34 HBeAg-negative patients and Group2 with 6 HBeAg-positive patients. Results: Twenty-one patients (52.5%) showed PC G1896A mutation and 11 (27.5%) carried A1762T/G1764A double mutations. These mutations were more frequent in HBeAg-negative patients than that in HBeAg-positive ones. Indeed, 58.8% of patients bearing G1896A mutation were HBeAg-negative while 16.7% were positive. In patients bearing T1762/A1764 double mutation, 29.4% were positive and 16.7% were negative. In addition, the A1896 mutation was restricted to HBV isolates that had wild-type T1858, while C1858 was rather linked to the occurrence of T1762/A1764 mutation. Interestingly, this study revealed a high frequency of genotype E. This frequency was important as compared to that of genotype D known to be predominant in the country as delineated in previous studies. Conclusions: Previous results supported and showed that HBV strains present in Tunisia belonging to genotype D and, to a lesser extent, to genotype E, were prone to mutations in BCP/ PC regions. This observation was more obvious in HBV isolates from asymptomatic chronic carriers (AsC). The high mutational rates observed in our study might result from a mechanism of viral escape that plays an important role in the loss of HBeAg. [ABSTRACT FROM AUTHOR]

Introduction. CD86 is a costimulatory molecule that participates in the regulation of T-cell lymphocytes activation. Thus, we examined a genetic marker on the CD86 gene in kidney transplant outcome. Materials and Methods. In our retrospective study, 168 kidney allograft recipients were genotyped by direct sequencing. Patients were classified into 2 groups of 29 human leukocyte antigen (HLA)- identical haplotype allograft recipients and 139 recipients showing one or more mismatches in the HLA haplotype. Forty-five patients (26.8%) developed at least 1 acute rejection (AR) episode, 7 in the first and 38 in the second group. Results. Acute rejection was associated with the presence anti-HLA antibodies before transplantation (P = .03). The AA genotype and A allele at position +1057 in the CD86 gene were more frequent in patients without AR (9.75% and 28.5%, respectively) compared with those showing an AR (2.22% and 23.3%, respectively). This difference was statistically significant in the anti-HLA-positive recipients, as AA frequency was 31.3% in non-AR patients and zero in AR ones (P = .04) and A allele frequency was 46.9% and 20.8%, respectively (P = .04). Patients bearing AA genotype reached a higher graft survival time (9.84 years) than those carrying GA (8.21 years, P = .32) or GG (7.61 years, P = .72) genotypes. Conclusion. These results suggest that AA genotype and A allele of CD86 +1057G>A polymorphism may confer a protection against acute kidney allograft rejection in Tunisian patients. [ABSTRACT FROM AUTHOR]

The present study describes the strains of hepatitis C virus (HCV) isolated from Tunisian hemodialysis patients. Thirty-three HCV strains isolated from different dialysis centers in Tunis City were amplified by RT-PCR in a region of the NS5b gene, genotyped by sequencing, and compared to international sequences by phylogenetic analysis. The phylogenetic tree showed that 16 HCV isolates have been identified as subtype 4k (48.5%), 7 as unspecified HCV-4 subtype (21.2%), 5 as subtype 4a et 1b (each 15.2%). The analysis of this tree revealed that the HCV-1b strains were closely related to Anglo-Saxon and European isolates, while the HCV-4 isolates are genetically similar to Egyptian and African strains. Phylogenic analysis of 33 Tunisian isolates with international HCV strains on a region of the NS5b gene demonstrated that the subtype 4k submerged the Tunis city and a new subtype of HCV4 seems to be suspect in this area.

Introduction: Our aim was to investigate the possibility of a significant relationship between chemokines and chemokine receptor genes polymorphisms and the spontaneous clearance or the persistence of HCV infection., Methods: A total of 96 hemodialysis (HD) patients infected with HCV were classified into two groups: G1 included 73 patients with persistently positive HCV-RNA and G2 included 23 HD patients who have spontaneously eliminated the virus. The control group consisted of 170 healthy blood donors. All subjects were genotyped for CCR5 ?32, CCR5 (-59029) A/G, CCR2 (64Ile) and MCP-1(-2518) A/G gene polymorphisms., Results: Our results showed a statistically significant increased frequencies of the CCR2 (64Ile) and the (-59029) CCR5 A alleles in patients infected with HCV (22.1% and 35.9%) compared to G1 (24.3% and 40.6%) and compared to controls (14.4% and 20%). We also observed a lower frequency of the MCP-1 G allele and a greater frequency of the CCR5?32 variant in G2 (15.2% and 6.5%) compared to G1 (22.6% and 1.4%) that was not statistically significant. However, adjustment for known covariates (age, gender and HCV genotypes) didn't confirm the results of univariate analysis., Conclusion: In conclusion, our study suggests a possible role for some of the studied chemokines polymorphisms in the spontaneous clearance or persistence of HCV infection in Tunisian population. These results should be further investigated by a prospective cohort studies and large population-based studies.

Aim: Interleukin (IL)-18 can regulate the Th2-mediated immune response and it may be involved in the pathogenesis of Th1 and Th2 chronic inflammatory diseases. This study sought to detect a possible association between two single nucleotide polymorphisms (SNPs) (-137G/C and -607C/A) in the IL-18 gene promoter region and susceptibility to inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population., Methods: The (-137G/C and -607C/A) IL-18 polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the sequence-specific polymerase chain reaction method., Results: The distribution of allele and genotype frequencies illustrate that the -137G/G genotype frequency was significantly higher in UC than in controls (p value corrected (pc) = 0.038). On the other hand, we found a statistically significant association (pc = 0.033) between genotype AA of the IL-18 gene promoter (-607C/A) polymorphism in UC patients and the distal localization of the lesions. In CD, no significant differences were observed at positions -607 and -137. The analysis of IBD patients according to clinical behavior revealed no difference., Conclusion: The two SNPs at position -607 (C/A) and -137 (G/C) in the promoter region of the IL-18 gene was associated with the development of UC but not CD, providing a strong support for an IBD susceptibility gene in the region surrounding IL-18. It remains to be determined precisely how the IL-18 alleles influence the pathogenesis of IBD., (Copyright © 2011 S. Karger AG, Basel.)

Background: Hepatitis viral C (HVC) is relatively frequent among kidney transplants. It is responsible for a morbid-mortality that compromises the results of transplantation in the medium and long term., Aim: To evaluate and to compare the prevalence of HVC, 172 kidney transplant adult patients were investigated in two Maghrebian centers at Casablanca (G1): 57 Moroccan patients and Tunisia (G2):.115 Tunisian patients. The impact of the HVC infection for a morbid-mortality was concerned only the Tunisian recipient patients: 20 kidney recipients having antibodies anti-VHC and positive HVC-RNA (Cases) which were matched in age, sex and date of the kidney graft, to 20 kidney transplant patients anti-HVC and VHCRNA negative (Controls)., Methods: The anti-VHC antibodies were detected by ELISA: Innogenetics and their positivity were confirmed by RIBAII. The ARN-VHC was analyzed by RT-PCR INNO-LiPA HCV II amplification of Innogenetics., Results: The prevalence of hepatitis C is similar for the two groups: 19.3% among Moroccan kidney transplants and 20.9% among Tunisians. The infection by the HVC was often active and the detection of viral RNA was found in 91.7% of the G2 patients against 50% among G1 patients. The genotype 1b is the most prevalent; it is found in 59% of the patients. The frequency of HVC among our kidney transplant patients is particularly determined by the duration and the mode of dialysis. In fact, 22.1% of the patients treated by hemodialysis are VHC (+) against 5,6% patients treated by peritoneal dialysis. Also, the average duration of the dialysis is 58,8 months for HVC (+) patients against 33.5 months for HVC (-) (p<0.0001) patients. The frequency of the chronic rejection of the graft is higher in the G2, but it is similar in Tunisian patients with or without antibodies anti-HVC. In the G1, this frequency is statistically higher among positive HVC transplant patients compared to the negative HVC grafted patients (p<0.05). The case-control study emphasizes the frequency of the proteinuria, the renal insufficiency, the mellitensis diabetes and the polyglobulinemia among patients HCV (+); however the differences between the two groups remain statistically non significant. The total rate of the hospitalizations is 26 per 100 patients per year in the HCV (+) group against 17 for the HCV (-). The average duration of hospitalizations is 72 days among HCV (+) patients against 30.2 days for the controls (p<0.05). The averages of survival of the patients and of the controls were similar 11.6±5.6 years for transplant patient HCV (+) against 11.2±5.5 years for the controls. The actuarial curves of the patients were not different for the patients having antibodies anti-HCV positive or negative., Conclusion: The blood and nosocomial modes of contamination of HVC infection explain their higher frequency in this population at risk. The mortality and the morbidity of the renal transplant patients infected by the HCV seem to be higher compared to the uninfected patients. A further study by large population should be carried out to confirm these results.

Aim: To assess the possible association between PTPN22 (R620W) gene polymorphism and inflammatory bowel disease (IBD)., Methods: One hundred and sixty-four patients with IBD [105 Crohn's disease (CD) and 59 ulcerative colitis (UC)] and 100 healthy controls were recruited. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by restriction fragment length polymorphism-polymerase chain reaction with RsaI digestion., Results: The genotypic and allelic frequencies of (R620W) PTPN22 gene polymorphism reveal a significant association of the PTPN22 620-W allele with IBD, compared to the healthy control group (OR: 17.81, 95% CI: 4.18-21.86, P = 0.00001). Nevertheless, no difference in this polymorphism was found between CD and UC patients. No significant association was found between the frequencies of genotypes of the PTPN22 gene with either the clinical features such as sex, age, age at disease onset, and extent of colitis, or the production of serological markers (anti-Saccharomyces cerevisiae antibody in CD and perinuclear anti-neutrophil cytoplasmic antibody in UC)., Conclusion: These observations confirm the association of IBD susceptibility with the PTPN22 1858T (620-W) allele in Tunisian patients.

Objective: The aim of this study was to determine the frequency of genotype and precore/core-promoter mutations in chronic hepatitis B virus (HBV) infected individuals in Tunisia., Methods: We studied 164 Tunisian patients (38 HBeAg-positive and 126 HBeAg-negative) with chronic HBV infection. Genotypes and precore/core-promoter mutations were studied using Inno-LiPA and Multiplex-PCR and PCR-RFLP methodology., Results: Alanine aminotransferase (ALT) levels were higher in HBeAg-positive compared with HBeAg-negative patients (p<0.05). Patients with HBeAg-positive chronic hepatitis B were younger than HBeAg-negative chronic hepatitis B patients. The 164 genotypes were distributed as follows: 1 genotype A (0.6%), 1 genotype B (0.6%), 3 genotype C (1.82%), 139 genotype D (84.75%), and 20 mixed genotypes (12.2%). In the precore region (41.5%) of the patients had exclusively PC mutant and (50.9%) had a mixture of wild-type and variant sequences. PC variant was more commonly found in HBeAg-negative patients than in HBeAg-positive patients (94.5% vs. 87.8%), respectively. The mutations in the core promoter were more common in HBeAg-negative patients (65.4%) than in HbeAg-positive patients (18.2%). These results indicate that genotype D is predominant in Tunisia. Precore mutation occurred invariably among HBeAg-positive and HBeAg-negative patients, whereas core-promoter mutations were more frequently found in HBeAg-negative patients., Conclusion: Analysis of these mutants may prove useful for clinical evaluation and choice of therapy.