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.

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.

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.

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.

Association of FV G1691A Polymorphism but not A4070G With Coronary Artery Disease.

Coronary artery disease (CAD) is one of the chief causes of death in the world. Several hypotheses have been promoted as for the origin of the disease, among which are genetic predispositions and/or environmental factors. The aim of this study was to determine the effect of factor V (FV) gene polymorphisms (Leiden, G1691A [FVL] and HR2 A4070G) and to analyze their association with traditional risk factors in assessing the risk of CAD. Our study population included 200 Tunisian patients with symptomatic CAD and a control group of 300 participants matched for age and sex. All participants were genotyped for the FVL and HR2 polymorphisms. Multivariate logistic regression was applied to analyze independent factors associated with the risk of CAD. Our analysis showed that the FVL A allele frequency ( P < 10-3, odds ratio [OR] = 2.81, 95% confidence interval [CI] = 1.6-4.9) and GA genotype ( P < 10-3, OR = 4.03, 95% CI = 2.1-7.6) are significantly more prevalent among patients with CAD compared to those controls and may be predisposing to CAD. We further found that the FVL mutation is an independent risk factor whose effect is not modified by other factors (smoking, diabetes, hypertension, dyslipidemia, and a family history of CAD) in increasing the risk of the disease. However, analysis of FV HR2 variation does not show any statistically significant association with CAD. The FVL polymorphism may be an independent risk factor for CAD. However, further investigations on these polymorphisms and their possible synergisms with traditional risk factors for CAD could help to ascertain better predictability for CAD susceptibility.

The Effect of ACE I/D Polymorphisms Alone and With Concomitant Risk Factors on Coronary Artery Disease.

BACKGROUND: Coronary artery disease (CAD), also known as atherosclerotic heart disease, is a leading cause of mortality and morbidity throughout the world. The role of insertion/deletion (I/D) polymorphisms of the angiotensin-converting enzyme (ACE) gene in the etiology of CAD remains to be more completely clarified. The aim of this study was to determine the role of the ACE I/D polymorphism in patients with CAD and to study the association together with traditional risk factors in assessing the risk of CAD. METHODS: Our study population included 145 Tunisian patients with symptomatic CAD and a control group of 300 people matched for age and sex. All participants in the study were genotyped for the ACE I/D polymorphisms obtained by polymerase chain reaction amplification on genomic DNA. RESULTS: Our analysis showed that the ACE D allele frequency ( P < 10-3; odds ratio [OR] = 5.2; 95% confidence interval [CI] = 3.6-7.6) and DD genotype ( P < 10-3; OR = 6.8; 95% CI = 4.4-10) are significantly more prevalent among patients with CAD than in controls and may be predisposing to CAD. We further found that the risk of CAD is greatly potentiated by several concomitant risk factors (smoking, diabetes, hypertension, dyslipidemia, and a family history of CAD). CONCLUSION: The ACE D allele may be predictive in individuals who may be at risk of developing CAD. Further investigations of these polymorphisms and their possible synergisms with traditional risk factors for CAD could help to ascertain better predictability for CAD susceptibility.

The Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and the Risk of Alzheimer's Disease.

OBJECTIVE: The aim of this study was to determine whether plasminogen activator inhibitor 1 (PAI-1) is associated with the risk of Alzheimer's disease (AD) in Tunisian patients. DESIGN AND METHODS: We analyzed the genotype and allele frequency distribution of the PAI-1 polymorphism in 60 Tunisian patients with AD and 120 healthy controls. RESULTS: The results show a significantly increased risk of AD in carriers of the 4G/4G and 4G/5G genotypes versus the wild-type 5G/5G genotype (4G/4G: 28.33% in patients vs 10.0% in controls; P < 10-3; OR = 8.78; 4G/5G: 55.0% in patients vs 38.33% in controls; OR = 4.45; P < 10-3). The 4G allele was also more frequently found in patients compared with controls; P < 10-3; OR = 3.07. For all participants and by gender, homozygotic carriers (4G/4G) were at an increased risk of AD over heterozygotes and women were at an increased risk over their male genotype counterparts. The odds ratio for AD among 4G/4G carriers for any group was approximately twice that of heterozygotes in the same group. Women homozygotes ranked highest for AD risk (OR = 20.8) and, in fact, women heterozygotes (OR = 9.03) ranked higher for risk than male homozygotes (OR = 6.12). CONCLUSION: These preliminary exploratory results should be confirmed in a larger study.

Role of the Apolipoprotein E Polymorphisms in the Development of Retinal Vein Occlusion in a Tunisian Population: A Case-Control Study.

Apolipoprotein E ( APOE) is a member of the apolipoprotein gene family. APOE is polymorphic with 3 main allelic types: ∊2, ∊3, and ∊4. Certain of these alleles have been associated with higher vascular risk. However, the association of APOE genotypes with retinal biomarkers and risk of retinal stroke is less clear. This study evaluated the role of APOE polymorphisms in retinal vein occlusion (RVO). In the present study, 2-point mutations coding amino acid residues 112 and 158 were amplified using the polymerase chain reaction (PCR) from DNA extracted from Tunisian participants. APOE genotypes were determined by multiplex PCR followed by molecular hybridization. Eighty-eight patients (26 women and 62 men) and 100 age- and gender-matched healthy participants were enrolled. The statistical study revealed a higher frequency of the ∊4 allele in patients as compared to controls (27.3% vs 9%) with a significant association of the ∊4 allele with the disease ( P < 10-3, Pa < 10-3, odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.1-6.8). The frequency of the ∊3 allele was significantly lower in the patients with RVO compared to the controls (60.2% vs 82.5%, respectively; P < 10-3, Pa < 10-3, OR = 0.32, 95% CI = 0.19-0.53). The ∊3 allele seems to be protective against the disease. There was no association between the APO ∊2 allele and RVO. The association of APOE allele and genotype with RVO requires further investigation in different populations.

Methylenetetrahydrofolate Reductase (MTHFR) (C677T and A1298C) Polymorphisms and Vascular Complications in Patients with Type 2 Diabetes.

OBJECTIVES: To assess whether 2 polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, are risk factors for vascular complications in Tunisian patients with type 2 diabetes mellitus. METHODS: The MTHFR polymorphisms were genotyped, and plasma homocysteine levels were evaluated in 160 Tunisian patients with type 2 diabetes mellitus. RESULTS: Prevalence of the 2 heterozygous polymorphisms of the thermolabile MTHFR gene (CT and AC) was encountered more commonly in patients with diabetes mellitus than in the healthy controls (p<10-3). Subjects with diabetes had significantly higher homocysteine (Hcy) levels than the control subjects; however, there was no statistical difference in plasma Hcy values between carriers of mutant genotypes (CT/TT for C677T and AC/CC for A1298C) and wild types (CC and AA) in patients with diabetes. Retinopathy was found to be a vascular complication in patients with either the 677CT or the 1298(AC+CC) genotype more commonly than in those with the wild-type genotypes (p=0.003; OR=3.2, 95% CI, 1.4 to 7.4; p<10-3; OR=5.9, 95% CI, 2.7 to 13). Only patients who carry the A1298C mutation (AC+CC) are at risk for at least 1 complication (p=0.002). Double heterozygous mutants were at the greatest risk for retinopathy and for suffering at least 1 complication (p<10-3). CONCLUSIONS: Studies involving a larger study population and various ethnic groups are required before ruling out the role of MTHFR gene in type 2 diabetes mellitus and in vascular complications.

Association Between Thrombophilic Gene Mutations and the Risk of Vascular Access Thrombosis in Hemodialysis Patients.

The cause of thrombosis in hemodialysis vascular access is considered to be of a multifactorial nature, including stenosis of the venous or arterial connection. 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 Factor V (G1691A and A4070G) and Factor II polymorphisms and vascular access thrombosis in hemodialysis patients. One hundred and twenty-one patients undergoing dialysis were selected as subjects. This sample was divided into two groups; a case group of 60 patients who had sustained one or more thrombotic events that resulted in vascular access failure and a control group of 61 patients, who never had a thrombotic occlusion of a functioning permanent dialysis access. Our data demonstrated a significantly increased risk of vascular access thrombosis in carriers of the mutant FV (G1691A and A4070G) polymorphisms (P < 0.05).Further studies on a large-scale population and other genetic variants will be needed to find candidate genes for vascular access thrombosis in hemodialysis patients.

Prothrombin G20210A and methylenetetrahydrofolate reductase C677T polymorphisms in peripheral capillary nonperfusion: a case report.

The G20210A mutation in the prothrombin gene is an established risk factor for venous thrombosis. However, there is some controversy as to the role played by this mutation in arterial thrombotic disease. The association of peripheral capillary nonperfusion with prothrombin G20210A mutation has never been reported before. We present the case of 34-year-old man who presented with peripheral capillary nonperfusion. The fundus examination of his right eye revealed an epiretinal membrane, peripheral (mainly temporally) retinal haemorrhages, exudates and microaneurismal alterations of the vascular bed. Fluorescein angiography of his right eye demonstrated an extended area of capillary nonperfusion distal to the microaneurismal lesions. Evaluation revealed mutations of the G20210A prothrombin and MTHFR genes. Screening for hereditary thrombophilia should be considered, regardless of patient age, in patients with peripheral retinal ischemia. The prothrombin G20210A mutation, a genetic risk factor, may be associated with peripheral capillary nonperfusion.

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 polymorphisms with schizophrenia in Tunisian patients.

BACKGROUND AND OBJECTIVES: The hypothesis that human leukocyte antigens (HLAs) confer susceptibility to schizophrenic disorders has been tested by studying linkage and association in family samples. Our goal was to evaluate the role of HLA in the risk of developing schizophrenia in a Tunisian population. DESIGN AND SETTINGS: Blood samples for this case-control study were collected from patients of the Department of Psychiatry at the Military Hospital of Tunisia between July 2012 and May 2013. METHODS: A total of 140 patients with schizophrenia were recruited for genetic analysis. Controls included 100 persons matched for age, sex, and risk factors. Participants were tested for HLA class II alleles. HLA-DRB1 and HLA-DQB1 alleles were genotyped using polymerase chain reaction sequence-specific primers. RESULTS: This study indicates that the alleles most responsible for disease susceptibility are DRB1*03 (P < 10-3) and DQB1*02 (P < 10-3) (P denotes probability values). The most protective alleles are DRB1*13 (P=.013) and DQB1*05 (P < 10-3). Further results revealed that DRB1*0301/DQB1*0201(P < 10-3), DRB1*0401/DQB1*0301 (P < 10-3) and DRB1*1101/DQB1*0301 (P < 10-3) are haplotypes most conducive to disease susceptibility. CONCLUSION: The present findings support an association between schizophrenia and the HLA-DR-DQ locus among a Tunisian population. To our knowledge, this is the first study performed to analyze the association of HLA DRB1/DQB1 alleles on schizophrenia susceptibility in Tunisia.

Association of methylenetetrahydrofolate reductase A1298C polymorphism but not of C677T with multiple sclerosis in Tunisian patients.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic neurological disease characterized by central nervous system (CNS) inflammation and demyelination of nerve axons. The aim of this study was to investigate a possible association between the methylenetetrahydrofolate reductase (MTHFR) gene and multiple sclerosis in Tunisian patients. PATIENTS AND METHODS: The genotyping of two missense variants of the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C was performed in 80 multiple sclerosis patients and 200 healthy controls. RESULTS: No significant differences were found in the frequency of the MTHFR C677T polymorphism between MS patients and healthy controls. 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); C/C: 13.75% versus 0%, p<10(-3), respectively). CONCLUSION: Although our preliminary findings suggest no association between the MTHFR C677T variants and MS, there is evidence to suggest a significant association between the MTHFR A1298C polymorphisms and MS.

Inherited thrombophilia-related complications in the treatment of a biatrial thrombus.

The study emphasizes the importance of the high risk of thromboembolism with inherited thrombophilic factors. Transesophageal echocardiography revealed large biatrial masses in an 87-year-old woman with history of nonvalvular atrial fibrillation, pulmonary embolism, and prescribed oral anticoagulation for prophylaxis of embolic events. The surgical removal of the presumed thrombus was declined by the patient and intravenous anticoagulation with unfractionated heparin was initiated. Treatment was complicated by additional embolic events and the patient succumbed after 14 days due to multiple organ failure. Testing revealed heterozygosity for both the factor V Leiden and the methylenetetrahydrofolate reductase C677T mutations inducing resistance to activated protein C. The combination of these thrombophilic factors can probably explain the poor anticoagulant response, embolic events, and the failure of resolution of the biatrial masses.

Role of methylenetetrahydrofolate reductase A1298C polymorphism in cerebral venous thrombosis.

The association between the methylenetetrahydrofolate reductase (MTHFR) gene and cerebral venous thrombosis (CVT) remains controversial. This study principally investigated the potential role of the MTHFR A1298C variant and CVT. The genotyping of the A1298C variant of the MTHFR gene was performed in 35 CVT patients and 200 healthy controls. The frequency of A1298C genotype among CVT patients was significantly higher compared with controls (P < 10(-3)), suggesting an association between this polymorphism and CVT. To our knowledge, there are no previous reports assessing the correlation between the MTHFR A1298C variant and CVT. Large study populations would be required to understand the contribution of this marker in the risk of CVT.