Najiba Fekih-Mrissa

Methylenetetrahydrofolate reductase (C677T and A1298C) polymorphisms, hyperhomocysteinemia, and ischemic stroke in Tunisian patients.

OBJECTIVE The present study evaluated the role of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C gene polymorphisms and correlated these results with plasma homocysteine (Hcy) levels in Tunisian ischemic stroke (IS) patients. METHODS Overall, 84 patients with IS were included and compared with 100 healthy controls. The most common stroke risk factors were investigated. Fasting plasma Hcy levels were measured. Genotyping of the MTHFR C677T and A1298 polymorphisms was studied by polymerase chain reaction. RESULTS Aside from tobacco and alcohol use, the other studied factors were significant risk factors for IS. Mean plasma Hcy levels were significantly higher in IS patients than in controls (16.1 ± 8.28 μmol/L versus 8.76 ± 3.48 μmol/L, P < 10(-3)). Significant associations were found with both the MTHFR 677(CT + TT) and 1298 (AC + CC) genotypes in comparison with controls (P < 10(-3)). A significant synergistic interaction was also found with the double heterozygote MTHFR 677CT/1298AC (P < 10(-3)). Homocysteine levels were significantly higher in IS patients with the MTHFR C677T variant (CT and TT genotypes) (P < 10(-3)); however, the difference was not significant with the MTHFR A1298C variant (AC and CC genotypes) (P = .31). CONCLUSION The MTHFR C677T and A1298 polymorphisms (individually or in concert) and hyperhomocysteinemia represent important risk factors for IS. Elevated Hcy levels were found to be associated with the MTHFR C677T variant; however, no significant association was found with the MTHFR A1298C variant.

Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer's disease

BACKGROUND Genetic risk factors play an important role in the pathogenesis of Alzheimers disease (AD). In this case-control study, we examined the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and their correlation with this pathology. OBJECTIVE To verify the association between MTHFR C677T and A1298C polymorphisms and Alzheimers disease. METHOD This work was conducted as a case-control study. Cases consisted of thirty-eight patients and 100 individuals without dementia constituted the control group. Genotyping of MTHFR polymorphisms was performed on patients and controls. RESULT Genetic analyses did not indicate a significant association between the MTHFR C677T mutation and AD (C/T: 63.15% versus 39%, p=0.087). However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p<10(-3)). Our data suggest an association between the MTHFR A1298C mutation and AD; however, the MTHFR C677T mutation did not contribute to susceptibility for AD. CONCLUSION The MTHFR A1298C polymorphism is a possible risk factor for Alzheimers disease.

Association of HLA-DR/DQ polymorphisms with Guillain–Barré syndrome in Tunisian patients

UNLABELLED Human leukocyte antigen (HLA) alleles have been implicated in many autoimmune diseases. The aim of this study is to assess whether HLA-DR/DQ alleles confer susceptibility to Guillain-Barré syndrome (GBS) in a Tunisian population. METHODS The HLA-DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers (PCR-SSP) in 38 patients with GBS and 100 healthy Tunisian control subjects. RESULTS GBS in Tunisian patients was found to be associated with the following alleles with these relative patient versus control frequencies (pc denotes Bonferroni corrected probability values): DRB1*13 (23.68% vs. 9.0%; pc=0.01), followed by DRB1*14 (22.36% vs.5.5%; pc<10(-3)). Two haplotypes, DRB1*14/DQB1*05 and DRB1*13/DQB1*03, were found to be associated with susceptibility to GBS. However DRB1*07/DQB1*02 and DRB1*03/DQB1*02 haplotypes were more frequently observed in controls than in patients (11.5% vs.7.9%; pc=0.007 and 23% vs. 5.26%; pc<10(-3) respectively). These haplotypes seem to confer protection against the disease. CONCLUSION Our data demonstrated a new GBS predisposition associated with HLA-DRB1*14 and DRB1*13. Theses alleles could be predisposing genetic factors for GBS in the Tunisian population.

Association of HLA-DR/DQ polymorphism with myasthenia gravis in Tunisian patients.

BACKGROUND AND OBJECTIVE Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction. MG has been shown to be associated with many human leukocyte antigens (HLA) in different populations. The aim of this study was to investigate the probable association between HLA-DR/DQ alleles and MG in Tunisian patients. PATIENTS AND METHODS HLA DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers (PCR-SSP) with 48 MG patients and 100 healthy individuals serving as the control group. RESULTS Myasthenia gravis in Tunisian patients was found to be associated with the following alleles (p(c) denotes Bonferroni corrected probability values): HLA-DRB1*03 (p(c)<10(-3)), DRB1*04 (p(c)=0.005), DQB1*02 (p(c)=0.002) and, DQB1*03 (p(c)=0.007). CONCLUSION Our data demonstrated a new HLA-MG predisposition with DRB1*04. The DRB1*03, DRB1*04, DQB1*02, and DQB1*03 alleles also could be predisposing genetic factors for MG in the Tunisian population.

Association of methylenetetrahydrofolate reductase (A1298C and C677T) polymorphisms with retinal vein occlusion in Tunisian patients

The role of two polymorphisms C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) gene in the etiology of retinal vein occlusion (RVO) has not been adequately clarified. The aim of this study was to examine the prevalence of these polymorphisms among RVO Tunisian patients with and without systemic risk factors. Seventy-two patients with retinal vein occlusion (RVO) were studied. The control group included140 people matched for age, sex, and risk factors. Participants in the study were genotyped for the MTHFR C677T and A1298C polymorphisms. The genotyping was performed by PCR-RFLP. No significant differences were found in the frequencies of the three genotypes (AA, AC, CC) of the MTHFR A1298C polymorphism between RVO patients and healthy controls. However, the prevalence of the group of mutated genotypes (AC+CC) of the missense variant MTHFR A1298C was significantly different between patients and controls (16.67% vs. 6.42%, p=.01). Additionally, the frequency of the CT genotype as well as the group of combined mutated genotypes (CT+TT) for the C677T variant was significantly higher among RVO patients compared with controls (p<10(-3), p<10(-3)). This suggests an association between this polymorphism and RVO. Large study populations would be required to understand more completely the contribution of these markers in the risk of RVO.

Association of HLA-DR/DQ Polymorphism With Alzheimer’s Disease

Background:Alzheimers disease (AD) is a complex disorder, resulting from an interaction between environmental and genetic factors. Several studies have addressed the association of AD with major histocompatibility complex (MHC) polymorphisms without arriving at any definite conclusions. The human leukocyte antigen (HLA) region is the key susceptibility locus in many immunological diseases. The aim of this study was to investigate the probable association between HLA-DR/DQ alleles and AD in Tunisian patients. Methods:HLA-DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers with 55 AD patients and 100 healthy individuals serving as the control group. Results:AD in Tunisian patients was found to be associated with the following alleles (Pc denotes Bonferroni corrected probability values): HLA-DRB1*15 (Pc < 10–3), DRB1*04 (Pc = 0.03) and DQB1*06 (Pc < 10–3). Two haplotypes found to be associated with the disease were DRB1*1501/DQB1*0602 (Pc < 10–3) and DRB1*0402/DQB1*0302 (Pc = 0.02). Conclusions:The authors believe this to be the first research linking the haplotypes DRB1*1501/DQB1*0602 and DRB1*04/DQB1*0302 with AD. Larger studies in other populations will be important to support the present findings of the possible susceptible risk of HLA-DR/DQ in AD.

Role of thrombophilia in vascular access thrombosis among chronic hemodialysis patients in Tunisia.

Vascular access thrombosis represents a serious and common problem in hemodialysis patients. Therefore, identification of relevant thrombotic risk factors could lead to an improved antithrombotic therapy. This case control study was performed to evaluate the relationship between some thrombophilias and vascular access thrombosis in hemodialysis patients. Seventy‐eight patients undergoing dialysis (between May 2007 and September 2009) were selected as subjects. This sample was divided into two groups; a case group of 28 patients who had sustained one or more thrombotic events that resulted in vascular access failure and a control group of 50 patients, who had never had a thrombotic occlusion of a functioning permanent dialysis access. Antithrombin, protein C and protein S levels were measured. Also, both groups were tested for the factor V Leiden mutation, the prothrombin G20210A mutation, the methylene tetrahydrofolate reductase C677T and A1298C mutations. Among genetic mutations of factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase genes, the C677T methylene tetrahydrofolate reductase mutation was the only significant genetic cause of vascular access thrombosis (P = 0.005). Our data demonstrated a significantly increased risk of vascular access thrombosis in carriers of the C677T methylene tetrahydrofolate reductase mutation.

The Status of Thrombophilic Defects and Non-O Blood Group as Risk Factors for Gestational Vascular Complications among Tunisian Women

Aims: Our objectives were to assess inherited thrombophilia and non-O blood group for the risk of gestational vascular complications among the Tunisian population. Methods: This study comprised 203 test subjects with adverse pregnancy outcomes including recurrent pregnancy loss, intra-uterine growth retardation, pre-eclampsia and placental abruption. Each subgroup was matched with 100 controls and analyzed separately. All patients were evaluated for factor V Leiden, factor II G20210A mutations and for non-O blood group. Protein S, protein C and antithrombin levels were determined and deficiencies noted. Results: The factor V Leiden mutation, non-O blood group and protein C deficiency had the highest incidences among patients both as a whole and in the 4 subgroups. The factor II G20210A mutation, protein S and antithrombin deficiencies were not statistically significant risk factors. Conclusion: Our results provide evidence for a significant association between the factor V mutation and placental abruption. Furthermore, we found that this and the non-O blood group independently increased the risk for intra-uterine growth retardation in our population.

Apolipoprotein E Genotypes Associated with Alzheimer Disease and Concomitant Stroke

BACKGROUND The ɛ4 allele of the apolipoprotein E (APOE) gene is a well-characterized genetic risk factor for Alzheimer disease (AD). The association between stroke and a higher risk for AD has also been reported. Our study sought to determine the relationship between the APOE gene and AD and the comorbid risk of stroke. METHODS The subjects of this study consisted of 48 patients with AD and 48 members of a control group. All subjects were genotyped for APOE. RESULTS The results clearly show a significant increased risk of AD in carriers of the APOE ε3/ε4 genotype (P = .003, odds ratio [OR] = 4.1) or ε4 allele (P = .001, OR = 4.2). The risk for stroke in AD patients was also increased for carriers of the APOE ε3/ε4 genotype (P = .02, OR = 9.0) and for carriers of the APOE ε4 allele (P = .004, OR = 5.5). CONCLUSIONS The present study is the first to establish a relationship between APOE ε4 and concomitant AD and stroke in the Tunisian population.

Association of HLA-DR/DQ polymorphism with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in Tunisian patients.

BACKGROUND AND OBJECTIVE Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder of the peripheral nervous system (PNS). The aim of this study was to investigate associations between HLA-DR/DQ alleles and CIDP in Tunisian patients. PATIENTS AND METHODS HLA DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers (PCR-SSP) with 36 CIDP patients and 100 healthy individuals serving as the control group. RESULTS CIDP in Tunisian patients was found to be associated with the HLA-DRB1*13 allele (pc=0.03) (where pc denotes the Bonferroni corrected probability value). Moreover, the two haplotypes, DRB1*13/DQB1*06 (22.22% of patients vs. 8.5% of controls, pc=0.017) and DRB1*07/DQB1*03 (13.88% of patients vs. 3% of controls, pc=0.005), were found to confer a susceptibility to CIDP. CONCLUSION To our knowledge, this is the first study performed to analyze the association of HLA-DRB1/DQB1 alleles on CIDP susceptibility in a Tunisian population.