Complement Component C3 Variant (R102G) and the Risk of Neovascular Age-Related Macular Degeneration in a Tunisian Population.

Purpose To explore the association between the polymorphism (S/F) p.R102G in the complement component 3 (C3) gene and age-related macular degeneration (AMD) in a Tunisian population. Methods The molecular study was performed by polymerase chain reaction using sequence-specific primers (PCR-SSP) in 207 control subjects free of any eye disease (fundus normal) and 145 patients with exudative AMD. The CH50 activity and quantification of C3 and C4 have been made by technical home method and nephelometry, respectively. Results The prevalence of C3 GG genotype polymorphism was significantly higher in AMD patients compared to controls (OR: 2.41, IC 95% [1.90-3.05], p = 0.0007). However, no correlation was found between this allelic variant and the type of neovascularization. Similarly, there is no association between this polymorphism and the presence of functional and/or quantitative hypocomplementemia. Conclusions The C3 GG genotype of the gene could be a susceptibility factor for AMD in the Tunisian population. However, it does not seem to influence the clinical profile of the disease.

MCP-1, CCR2 and CCR5 polymorphisms in Tunisian patients with atopic asthma.

Chemokines and their receptors play an important role in the late inflammatory stage of asthma. In this study, we aimed to investigate polymorphisms of MCP-1 (CCL2), CCR2 and CCR5 which can affect qualitatively and/or quantitatively their production and thus influence both susceptibility and severity of asthma and its clinical and biological features.MCP-1 (A/G -2518), CCR2 (+/64I), CCR5 (G/A -59029) and CCR5 (∆32) polymorphisms were evaluated by PCR in 107 Tunisian patients with asthma and 169 healthy controls.No significant association was found between the four investigated polymorphisms and asthma. Nevertheless the haplotype MCP1*AG/CCR2*+/+ was significantly l ess frequent in patients (20.5%) compared to controls (32.5%) (p=0.03; OR=0.54; 95% CI: 0.29-0.98). Whereas no difference was observed in CCR2/CCR5 haplotypes between patients and controls. Analysis of polymorphisms with clinical and biological features showed that the concomitant presence of MCP-1*G/CCR2*64I alleles was less frequent in severe forms (4.34%) compared to moderate disease (12%) but the difference was not significant (p=0.27). No association was observed between the four polymorphisms and the presence of atopic rhinitis or atopic conjunctivitis and an elevated rate of serum IgE over 200 IU/ml.Additional effects of MCP-1 and its receptor CCR2 polymorphisms seem to be involved in disease susceptibility to asthma in Tunisian patients; nevertheless they could be protective against its severe forms.

Phylogenetic analysis of isolated HCV strains from tunisian hemodialysis patients.

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.

Investigation of DNA sequence in the Basal core promoter, precore, and core regions of hepatitis B virus from Tunisia shows a shift in genotype prevalence.

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.

[Hepatitis C in kidney transplantation: comparative study between two Maghrebin centers: Casablanca and Tunis]. / L'hépatite virale C au cours de la transplantation rénale: étude comparative entre deux centres Maghrébins: Casablanca et Tunis.

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.

Polymorphism in ICAM-1, PECAM-1, E-selectin, and L-selectin genes in Tunisian patients with inflammatory bowel disease.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are chronic intestinal disorders characterized by immune dysregulation and leukocytes recruitment into gastrointestinal tract. Cell adhesion molecules (CAM) mediate the extravasation of leukocytes and their accumulation in inflamed intestinal mucosa. Recently, CAM genes have been implicated in determining susceptibility to UC and CD. We investigate seven mutations in CAM: G241R and K469E in ICAM-1, V125L in PECAM-1, G98T, S128R, and L554F in E-selectin and F206L in L-selectin in 197 Tunisian patients (73 with UC and 124 with CD) and 194 controls. These polymorphisms were detected by polymerase chain reaction sequence-specific primers and restriction enzyme analysis. RESULTS: A significant increase in allele frequencies of 206L of L-selectin and the associated genotype F/L was observed in both patients with UC and CD compared with controls. Subgroup analysis showed that the L206 allele and F/L206 genotype frequencies were significantly increased in UC patients with left-sided type; whereas, the F/L206 genotype was significant in CD patients with ileocolonic location and stricturing behavior compared with controls. No significant differences in allele or genotype frequencies were observed for ICAM-1 K469E, E-selectin, and PECAM-1 polymorphisms between UC patients, CD patients, and controls. CONCLUSION: We found an association of inflammatory bowel disease with allele L206 of L-selectin gene, whereas genotype L/F was associated with a subgroup of UC (left-sided type) and CD patients with more extensive location of disease and stricturing behavior. However, further studies are needed to confirm our findings.

Human platelet antigens polymorphisms and susceptibility of thrombosis in hemodialysis patients.

To investigate the association between the polymorphisms of human platelet antigen (HPA)-1,2,3,4,5 and susceptibility to develop thrombosis accident in arteriovenous fistula (AVF), genomic DNA of 112 hemodialysis (HD) patients and 100 healthy blood donors were genotyped by PCR-SSP. The patients were classified into 2 groups: G1 included 54 HD patients presented at least one thrombotic episode on the level of the AVF, and G2 included 58 HD patients without any episode of thrombosis. The allelic frequencies of HPA-1, 2, 3, and 5 among patients and controls did not reveal significant differences. However, the HPA-4b allele was significantly more frequent in G1 than in controls or in G2 patients (23.1% vs. 11.5% and 0.9%, respectively), p<0.01 and p<0.001. The genotype distribution of HPA-4 polymorphism reveals that the HPA-4a4b genotype was more frequent in G1 patients (23/54: 42.6%) than in all HD patients (25/112: 22.3%) or in G2 patients (1/58: 1.72%) (p<0.001, odds ratio: 45.6). Among 24 HD patients with HPA-4a4b genotype, 23 (96%) developed at least 1 or more thrombotic episode on the level of their AVF. However, 30 patients (34.5%) among 87 HD patients with HPA-4a4a genotype presented thrombotic episode (p<0.001). These results reveal a significant association between HPA-4a4b and thrombosis, and it is likely that HPA polymorphisms could be useful markers for potential risk of thrombosis in hemodialysis.