HLA DRB1*03 as a possible common etiology of schizophrenia, Graves' disease, and type 2 diabetes.

BACKGROUND: Autoimmune diseases and schizophrenia share many common features. Association studies confirm a shared genetic association in the human leukocyte antigen (HLA) region between schizophrenia and most autoimmune diseases. To our knowledge, the simultaneous syndromes of Graves' disease (GD) and type 2 diabetes (T2D) in schizophrenia are rare in Tunisia. CASE PRESENTATION: We report a case of a 42-year-old woman admitted to the department of psychiatry for an acute relapse of chronic schizophrenia. Her medical history revealed that she was followed for Graves' disease and for a type 2 diabetes mellitus. A low-resolution HLA typing was performed by polymerase chain reaction sequence-specific primer (PCR-SSP) techniques according to determine the patient's haplotype. CONCLUSIONS: Our study suggests that the HLA DRB1*03 allele may explain a common etiology underlying the co-morbidity of Graves' disease, type 2 diabetes, and schizophrenia in our patient.

Association between an angiotensin-converting enzyme gene polymorphism and Alzheimer's disease in a Tunisian population.

BACKGROUND: The angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D or indel) polymorphism has long been linked to Alzheimer's disease (AD), but the interpretation of established data remains controversial. The aim of this study was to determine whether the angiotensin-converting enzyme is associated with the risk of Alzheimer's disease in Tunisian patients. METHODS: We analyzed the genotype and allele frequency distribution of the ACE I/D gene polymorphism in 60 Tunisian AD patients and 120 healthy controls. RESULTS: There is a significantly increased risk of AD in carriers of the D/D genotype (51.67% in patients vs. 31.67% in controls; p = .008, OR = 2.32). The D allele was also more frequently found in patients compared with controls (71.67% vs. 56.25%; p = .003, OR = 2.0). Moreover, as assessed by the Mini-Mental State Examination, patient D/D carriers were more frequently found to score in the severe category of dementia (65%) as compared to the moderate category (32%) or mild category (3%). CONCLUSIONS: The D/D genotype and D allele of the ACE I/D polymorphism were associated with an increased risk in the development of AD in a Tunisian population. Furthermore, at the time of patient evaluation (average age 75 years), patients suffering with severe dementia were found predominantly in D/D carriers and, conversely, the D/D genotype and D allele were more frequently found in AD patients with severe dementia. These preliminary exploratory results should be confirmed in larger studies and further work is required to explore and interpret possible alternative findings in diverse populations.

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.

Thrombophilic risk factors in different types of retinal vein occlusion in Tunisian patients.

BACKGROUND: Retinal vein occlusion (RVO) is the second most common cause of vision loss because of retinal vascular disease. There are 2 types of RVO: branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). The pathogenesis of RVO is multifactorial. The role of factor V Leiden (FVL) and prothrombin mutations was examined in patients with CRVO and BRVO. METHODS: FVL and prothrombin were investigated by extracting DNA of 88 patients with RVO. Sixteen of the patients were diagnosed with CRVO, 4 with hemispheric retinal vein occlusion, and 68 with BRVO. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Significant differences were found in the frequencies of the genotypes for both the FVL (G1691A) (P<10(-3), odds ratio [OR]=17.4, confidence interval [CI]=6.20-59) and prothrombin (G20210A) (P=.007, OR=5.11, CI=1.30-29) polymorphisms between RVO patients and healthy controls. Additionally, the frequency of the GA genotype for the G1691A polymorphism was significantly higher among the patients in a subset of BRVO compared with controls (P<10(-3), OR=21.4, CI=7.34-74.2). However, no statistically significant differences were found in the frequencies of the prothrombin G20210A polymorphism between the BRVO group and healthy controls (P=.09, OR=3.13, CI=64-19.9). The frequency of both G1691A and G20210A genotypes among the patients of a CRVO subgroup was significantly higher compared with controls (P<10(-3), OR=11.4, CI=2.94-44.2; P=.007, OR=10.8, CI=2.15-54.1, respectively), suggesting an association between these polymorphisms and CRVO. CONCLUSIONS: Large study would be required to understand completely the contribution of these markers in the risk of all types of RVO.

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.

Association of HLA-DR-DQ polymorphisms with diabetes in Tunisian patients.

OBJECTIVE: Type 1 diabetes (T1D) is a polygenic disease whose principal locus is the human leukocytes antigen (HLA) region. The aim of this study was to evaluate HLA DR-DQ alleles and to asses them as risk factors for type 1 diabetes in the Tunisian population. MATERIALS AND METHODS: A total of 119 subjects with diabetes were tested for HLA class II alleles and compared with 292 healthy controls. HLA DRB1 and DQB1 alleles were genotyped using polymerase chain reaction sequence-specific primers (PCR-SSPs). RESULTS: The results revealed that the most susceptible haplotypes are the DRB1(*)03-DQB1(*)02 (pc<10(-3)) and DRB1(*)0401-DQB1(*)0302 (pc=0.001). (pc denotes Bonferroni corrected probability values.) The most protective haplotypes are DRB1(*)11-DQB1(*)03, DRB1(*)07-DQB1(*)02, and DRB1(*)13-DQB1(*)06 (pc=0.0026, pc=0.0065, and pc=0.02 respectively). Our results showed some particularities unique to Tunisians, there was a lack of a significant protective effect of the DRB1(*)15-DQB1(*)06 haplotype that usually is the dominant combination associated with protection in most other populations. CONCLUSION: Tunisian diabetic patients share the most susceptible and protective HLA haplotypes with Caucasians and those in neighbor Mediterranean countries. This is most likely explained by the history and admixture events of Tunisia and North Africa.

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.

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.

[Disseminated intravascular coagulation: role of the International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring system]. / La coagulation intravasculaire disséminée: intérêt du score de la société internationale sur la thrombose et l´hémostase.

Disseminated intravascular coagulation (DIC) is a life-threatening event during resuscitation. The International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring system enables early diagnosis of DIC. We here report three clinical cases of DIC characterized by several etiologies: prostatic adenocarcinoma, septic shock and retroplacental hematoma. The tests of hemostasis needed to calculate international society on thrombosis and haemostasis (ISTH) score (platelet count, prothrombin ratio, values of fibrinogen and D-dimer levels) were performed regularly. Additional, complementary tests (soluble complexes test, euglobulin lysis test, antithrombin level dosing, activated protein C and factor V dosing) were also performed. ISTH score enables early diagnosis of DIC.