RESUMO
Background: Central retinal artery occlusion (CRAO) is a medical condition characterized by sudden blockage of the central retinal artery, which leads to a significant and often irreversible loss of vision. Observational studies have indicated that diabetes mellitus is a risk factor for CRAO; however, there is no research on the causal relationship between diabetes mellitus, particularly type 2 diabetes, and CRAO. This study aimed to perform Mendelian randomization (MR) analysis to clarify the causal relationship between type 2 diabetes and CRAO. Methods: Genetic variants associated with type 2 diabetes were selected from two different datasets. A recent genome-wide association study of CRAO conducted using the FinnGen database was used as the outcome data. A two-sample MR was performed to evaluate the causal relationship between type 2 diabetes and CRAO. Inverse variance weighting was the primary method, and MR-Egger, maximum likelihood, and median weighting were used as complementary methods. A multivariate MR (MVMR) analysis was performed to further evaluate the robustness of the results. Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test were used for the sensitivity analyses. Results: Genetically predicted type 2 diabetes was causally associated with CRAO(odds ratio [OR] =2.108, 95% confidence interval [CI]: 1.221-3.638, P=7.423×10-3), which was consistent with the results from the validation dataset (OR=1.398, 95%CI: 1.015-1.925, P=0.040). The MVMR analysis suggested that type 2 diabetes may be an independent risk factor for CRAO (adjusted OR=1.696; 95%CI=1.150-2.500; P=7.655×10-3), which was assumed by the validation dataset (adjusted OR=1.356; 95%CI=1.015-1.812; P=0.039). Conclusion: Our results show that genetically predicted type 2 diabetes may be causally associated with CRAO in European populations. This suggests that preventing and controlling type 2 diabetes may reduce the risk of CRAO.
Assuntos
Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Oclusão da Artéria Retiniana , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Humanos , Oclusão da Artéria Retiniana/genética , Oclusão da Artéria Retiniana/epidemiologia , Oclusão da Artéria Retiniana/complicações , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Predisposição Genética para DoençaRESUMO
INTRODUCTION: Increasing evidence implicates retinal vascular occlusions as a susceptibility factor for cardiovascular diseases (CVDs), whereas inconsistent results on the relationship were reported in previous observational studies. This research using a bidirectional two-sample Mendelian randomization (MR) analysis aimed to investigate the potential association between genetically determined central/branch retinal artery and retinal vein occlusions (CRAO/BRAO/RVO) and the risk of CVD. METHODS: Summary statistics of retinal vascular occlusions from the largest available genome-wide association study of European descent were used to investigate their relationship with CVDs, and vice versa. Primary analyses were conducted using the common inverse-variance weighted approach. Several complementary sensitivity analyses were performed to verify the reliability of our results. RESULTS: Inverse variance weighted method showed suggestive effects of genetically determined RVO on ischemic stroke (IS) (odds ratio [OR] = 1.021, 95% confidence [CI] = 1.004-1.037, p = 0.012), a genetic liability to CRAO increased the risk of myocardial infarction (MI) (OR = 1.014, 95% CI = 1.006-1.023, p = 7.0 × 10-4). In addition, genetic predisposition to BRAO had a positive effect on stroke (OR = 1.008, 95% CI = 1.002-1.013, p = 0.011), IS (OR = 1.007, 95% CI = 1.001-1.014, p = 0.022), and cardioembolic stroke (CES) (OR = 1.018, 95% CI = 1.006-1.031, p = 0.004). The point estimates from sensitivity analyses were in the same direction. Reverse MR analyses found no significant evidence for the effect of CVDs on retinal vascular occlusions. CONCLUSION: Our MR study provides potential evidence that retinal vascular occlusions are causally linked to increased risk of CVDs including IS, MI, stroke, and CES. This supports the need for clinical CVD screening in individuals with retinal vascular occlusions. Further investigations are warranted to clarify the effects of CVDs on ocular comorbidities.
Assuntos
Doenças Cardiovasculares , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/genética , Doenças Cardiovasculares/genética , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Oclusão da Artéria Retiniana/genéticaAssuntos
Oclusão da Artéria Retiniana , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Oclusão da Artéria Retiniana/tratamento farmacológico , Oclusão da Artéria Retiniana/genética , Fibrinólise , Terapia Trombolítica , Resultado do Tratamento , Infarto da Artéria Cerebral Média/tratamento farmacológicoRESUMO
PURPOSE: Report the case of a patient with a history of central retinal artery occlusion in her right eye and amaurosis fugax associated with acute ischemic changes in her left eye related to a prothrombin G20210A gene variant, in which OCT-A was used as a diagnostic and therapeutic tool. CASE PRESENTATION: 55-year-old woman with a history of central retinal artery occlusion in her right eye and prothrombin gene G20210A (F2) variant diagnosis. She presented to our consultation with amaurosis fugax in her left eye. As medical history, she had an episode of bilateral posterior scleritis diagnosed asynchronously with the current episode. Vascular, autoimmune, and metabolic prothrombotic diseases were ruled out. OCT-A showed areas suggesting acute ischemia consistent with macular retinopathy in her left eye. Anticoagulant therapy with Apixaban was initiated, considering the risk for her vision. Control OCT-A showed perfusion improvement in the previous site of the occlusive vascular event. We also considered the extent of the inflammatory response due to posterior scleritis as a differential diagnosis. Nevertheless, it is less likely, considering the temporality between scleritis and the retinal-vascular episodes. CONCLUSIONS: While the G20210A prothrombin gene (F2) variant is a rare cause of retinal artery occlusion, it is important to consider it a differential diagnosis. Good visual outcomes can be achieved with prompt initiation of antithrombotic treatment. In addition, OCT-A is useful for diagnosing ischemic retinal changes that cannot be observed with other diagnostic methods and monitoring them.
Assuntos
Oclusão da Artéria Retiniana , Esclerite , Amaurose Fugaz/etiologia , Amaurose Fugaz/genética , Anticoagulantes , Feminino , Fibrinolíticos , Humanos , Pessoa de Meia-Idade , Protrombina/genética , Retina , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/tratamento farmacológico , Oclusão da Artéria Retiniana/genética , Esclerite/complicaçõesRESUMO
Background: Central retinal artery occlusion (CRAO) is a rare ocular-ischemic syndrome causing irreversible blindness. Its pathophysiology has not been clarified, and no targeted therapies are available yet. Hyperbaric oxygen (HBO2) therapy is already an approved therapy for CRAO and has been shown to improve the visual acuity of CRAO patients safely. However, further clinical data are required to classify HBO2 therapy as a type-I general agreement for CRAO. Materials and Methods: Eleven patients with non-arteritic CRAO were enrolled. Patient demographics, medical history, detailed eye examinations, HBO2 therapy results, pre-/post HBO2 therapy visual acuity measurements and genotypes for common thrombophilic mutations (Factor V G1691A Leiden, Factor II G20210A, MTHFR A1298C, MTHFR C677T, and PAI-1-675 4G/5G) were obtained. Result: Six patients (54%) responded to HBO2 therapy compared to five non-responders (46%). Patients admitted before 12 hours responded well to HBO2 therapy. No systemic diseases nor advanced age were statistically correlated to CRAO. A combination of mutations rather than single mutations for each patient could be seen as responsible for CRAO. No Factor V G1691A Leiden mutations and only one FII G20210A mutation were observed. Eight patients (72%) had MTHFR 677T allele, five patients (45%) had MTHFR 1298C allele, and 10 patients (91%) had the PAI-1-675 4G allele. Conclusion: Not a single mutation but a combination of mutations and other unknown factors probably lead to CRAO, and if intervention is timely, HBO2 therapy offers improvement in visual acuity safely.
Assuntos
Oxigenoterapia Hiperbárica , Mutação , Oclusão da Artéria Retiniana/genética , Oclusão da Artéria Retiniana/terapia , Adulto , Idoso , Fator V/genética , Feminino , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/genética , Protrombina/genética , Tempo para o Tratamento , Resultado do Tratamento , TurquiaRESUMO
Factor V is a pro-coagulant cofactor required for the transformation of prothrombin into thrombin. Thrombin activates factor V, which is then deactivated by protein C. A mutation in factor V is responsible for the formation of factor V Leiden, resistant to activated protein C. The association of this mutation with venous thromboses has been established. Its association with arterial occlusions is still controversial. We report the case of a central retinal artery occlusion associated with a non-arteritic anterior optic neuropathy associated with a Leiden mutation of factor V (FVL). The presence of FVL has been associated with lack of reperfusion and rapid progression to neovascularization. It seems that FVL intervenes mainly during the reperfusion phase after the occurrence of arterial thrombosis.
Assuntos
Resistência à Proteína C Ativada/diagnóstico , Fator V/genética , Mutação , Neuropatia Óptica Isquêmica/diagnóstico , Oclusão da Artéria Retiniana/diagnóstico , Resistência à Proteína C Ativada/complicações , Resistência à Proteína C Ativada/genética , Angiofluoresceinografia , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Neuropatia Óptica Isquêmica/complicações , Neuropatia Óptica Isquêmica/genética , Oclusão da Artéria Retiniana/complicações , Oclusão da Artéria Retiniana/genética , Tomografia de Coerência ÓpticaRESUMO
BACKGROUND: Waardenburg syndrome (WS) is a very rare genetic disorder affecting the neural crest cells. Coexistence of branch retinal vein occlusion (BRVO) and branch retinal artery occlusion (BRAO) in the same eye is also a rare finding. Here we report a case of WS type 1 that was confirmed by a novel mutation with the finding of unilateral BRVO and BRAO. CASE PRESENTATION: A 36-year-old, white-haired Korean man presented with a complaint of loss of vision in the inferior visual field of his right eye and hearing loss. He had telecanthus with a medial eyebrow and a hypochromic left iris. Funduscopy showed an ischemic change at the posterior pole in the right eye with sparing of the foveal center as well as retinal hemorrhages and white patches along the superotemporal arcade. Fundus angiography revealed the presence of both BRVO and BRAO, and optical coherence tomography showed thickening and opacification of the retinal layers corresponding to the ischemic area. A blood workup revealed hyperhomocysteinemia and the presence of antiphospholipid antibodies; both are suggestive as the cause of the BRVO and BRAO. Single nucleotide polymorphism analysis confirmed a novel PAX3 mutation at 2q35 (c.91-95 ACTCC deletion causing a frameshift). These findings confirmed a diagnosis of WS type 1. CONCLUSIONS: WS is a heterogeneous inherited disorder of the neural crest cells that causes pigment abnormalities and sensorineural hearing loss. This is the first report of unilateral BRVO and BRAO in a patient with WS. Furthermore, the PAX3 mutation identified in this patient has not been reported previously.
Assuntos
DNA/genética , Mutação , Fator de Transcrição PAX3/genética , Oclusão da Artéria Retiniana/genética , Oclusão da Veia Retiniana/genética , Síndrome de Waardenburg/genética , Adulto , Análise Mutacional de DNA , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Fator de Transcrição PAX3/metabolismo , Linhagem , República da Coreia , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/metabolismo , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/metabolismo , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Síndrome de Waardenburg/diagnósticoRESUMO
Inherited hypercoagulable states (i.e. thrombophilia) have been suggested to be involved in retinal vascular occlusion but results are divergent. Vascular micronutrition and ischemia have been hypothesised to be involved in the pathogenesis of glaucoma. This nationwide study determines the importance of family history of venous thromboembolism (VTE) as a risk factor for retinal vein occlusion (RVO), retinal artery occlusion (RAO), primary open angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). A total of 6,007,042 Swedish individuals were studied. Data from the Swedish Multigeneration Register for subjects aged 0-78 years old for the period 1997-2010 were linked to the Swedish Hospital Discharge Register and the Hospital Outpatient Register. Main exposure measure was family history of VTE in first-degree relatives (parents and/or siblings). Main outcomes were hazard ratios (HRs) for RVO, RAO, POAG, and PACG. During follow-up 9036 individuals developed RVO, 2137 individuals developed RAO, 29,176 individuals developed POAG and 1498 individuals developed PACG. There was no association between family history of VTE and risk of RVO (HR = 1.04, 95 % CI 0.98-1.10), RAO (HR = 1.00, 95 % CI 0.89-1.13), POAG (HR = 0.96, 95 % CI 0.93-0.99), and PACG (HR = 0.92, 95 % CI 0.80-1.06) in the crude age and sex adjusted model. The results were similar in the fully adjusted model: RVO (HR = 1.04, 95 % CI 0.99-1.11), RAO (HR = 1.01, 95 % CI 0.89-1.13), POAG (HR = 0.97, 95 % CI 0.94-1.00), and PACG (HR = 0.91, 95 % CI 0.79-1.05). Family history of VTE is not a risk factor for RVO, RAO, POAG and PACG. Thus, it is unlikely that strong and common genetic variants associated with VTE are of importance for these disorders.
Assuntos
Família , Predisposição Genética para Doença , Glaucoma de Ângulo Fechado , Glaucoma de Ângulo Aberto , Sistema de Registros , Oclusão da Artéria Retiniana , Oclusão da Veia Retiniana , Tromboembolia Venosa , Feminino , Seguimentos , Glaucoma de Ângulo Fechado/complicações , Glaucoma de Ângulo Fechado/epidemiologia , Glaucoma de Ângulo Fechado/genética , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/epidemiologia , Glaucoma de Ângulo Aberto/genética , Humanos , Masculino , Oclusão da Artéria Retiniana/complicações , Oclusão da Artéria Retiniana/epidemiologia , Oclusão da Artéria Retiniana/genética , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/epidemiologia , Oclusão da Veia Retiniana/genética , Fatores de Risco , Suécia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/genéticaAssuntos
Actinas/genética , Mutação de Sentido Incorreto , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/genética , Adolescente , Dilatação Patológica/diagnóstico , Angiofluoresceinografia , Humanos , Masculino , Oftalmoscopia , Vasos Retinianos/patologia , Tomografia Computadorizada por Raios XRESUMO
In recent years, more and more attention has been paid to the role of polymorphisms in genes that code for the components of vitamin K cycle in the development of retinal vascular occlusion. Vitamin K serves as a cofactor for a number of blood coagulation factors, namely, factor II, VII, IX, and X, and also for anticoagulation proteins C and S. According to the literature, 1639G4A polymorphism of the vitamin K epoxide reductase complex subunit 1 gene (VKORC1) is likely to be a new risk factor of retinal vascular occlusion.
Assuntos
Oclusão da Artéria Retiniana/genética , Oclusão da Veia Retiniana/genética , Vitamina K Epóxido Redutases/genética , Vitamina K/metabolismo , Coagulação Sanguínea/genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Apelin activity plays a role in regulating blood pressure. This study explored the relationship between single nucleotide polymorphisms (SNPs) in the Apelin gene (APLN) with hypertension and hypertension with central retinal artery equivalent (CRAE) stenosis in a coastal Chinese population. All subjects answered an epidemiological survey for demographic and disease characteristics. Apelin levels were determined and three APLN SNPs, rs56204867, rs3115757, and rs3761581, were evaluated. CRAE was measured using fundus photography. Apelin levels were significantly lower in subjects with hypertension and hypertension with CRAE stenosis (0.23 ± 0.10 ng/ml and 0.21 ± 0.08 ng/ml, respectively) compared with control subjects (0.25 ± 0.11 ng/ml; p < 0.001). Linear regression analysis showed hypertension and hypertension with CRAE stenosis was associated with age, being male, systolic blood pressure, abnormal blood lipids, and Apelin levels. Genetic analysis indicated that in both males and females SNP rs3761581 was associated with hypertension and that more males carrying rs56204867 and rs3761581 T-A haplotype had hypertension (61.88%) and hypertension with CRAE stenosis (56.82%) than control males (39.33%). In this Chinese population, Apelin and APLN SNP rs3761581 was associated with combined hypertension with CRAE, indicating that the expression of APLN gene products may be involved in vascular injury.
Assuntos
DNA/genética , Hipertensão/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Polimorfismo de Nucleotídeo Único , Oclusão da Artéria Retiniana/genética , Apelina , Pressão Sanguínea/fisiologia , China/epidemiologia , Feminino , Genótipo , Haplótipos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Incidência , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Oclusão da Artéria Retiniana/complicações , Oclusão da Artéria Retiniana/epidemiologiaRESUMO
BACKGROUND: We describe a child with central retinal artery occlusion and hyperhomocysteinemia. METHODS: A 13-year-old girl developed sudden vision loss and was hospitalized for diagnosis and treatment. RESULTS: Her physical examination was normal except for her ophthalmologic examination. Her serum homocysteine level and lipoprotein(a) were elevated to 45.27 µmol/L and 61 mg/dL 0-29 mg/dL, respectively. A homozygous mutation was identified for methylenetetrahydrofolate reductase at position C677T. CONCLUSION: This report documents central retinal artery occlusion associated with the risk factors of hyperhomocysteinemia caused by methylenetetrahydrofolate reductase C677 T mutation and high lipoprotein(a) level in a child. Retinal artery occlusion is rare in children. This patient emphasizes the need for a systemic evaluation for hyperhomocysteinemia and lipoprotein(a) levels in children with retinal vascular occlusion of uncertain etiology.
Assuntos
Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/complicações , Lipoproteína(a)/sangue , Oclusão da Artéria Retiniana/sangue , Oclusão da Artéria Retiniana/etiologia , Adolescente , Feminino , Angiofluoresceinografia , Humanos , Hiper-Homocisteinemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação/genética , Papiledema/patologia , Oclusão da Artéria Retiniana/genética , Tomografia de Coerência ÓpticaAssuntos
Doença de Fabry/complicações , Heterozigoto , Oclusão da Artéria Retiniana/etiologia , Adolescente , Adulto , Cegueira/diagnóstico , Doença de Fabry/enzimologia , Doença de Fabry/genética , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Oclusão da Artéria Retiniana/enzimologia , Oclusão da Artéria Retiniana/genética , Adulto Jovem , alfa-Galactosidase/metabolismoRESUMO
We prospectively assessed associations of thrombophilia- hypofibrinolysis with central retinal vein occlusion (CRVO) (40 patients) and central retinal artery occlusion (CRAO) (9 patients). We used polymerase chain reaction measures for thrombophilia (factor V Leiden, prothrombin, C677T MTHFR, platelet glycoprotein PlA1/A2) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G). Serologic thrombophilia measures included protein C, protein S (total and free) and antithrombin III, homocysteine, lupus anticoagulant, anticardiolipin antibodies IgG-IgM, and factors VIII and XI. Serologic hypofibrinolysis measures included Lp(a) and plasminogen activator inhibitor activity. For comparison with 40 CRVO and 9 CRAO patients, 80 and 45 race-gender matched controls were studied. The factor V mutation was more common in CRVO (3/40, 8%) than controls (0/79, 0%), P = .036, as was high (>150%) factor VIII (12/40, 30%) versus (4/77, 5%), P = .0002. Low antithrombin III (<80%) was more common in CRVO (5/39, 13%) than in controls (2/73, 3%), P = .049. Homocysteine was high (> or =13.5 micromol/L) in 5/39 (13%) CRVO patients versus 2/78 controls (3%), P = .04. Three of 9 CRAO patients (33%) had low (<73%) protein C versus 2/37 controls (5%), P = .044. Two of 9 CRAO patients (22%) had high (> or =13.5 micromol/L) homocysteine versus 0/42 controls (0%), P =. 028. Four of 9 CRAO patients had the lupus anticoagulant (44%) versus 4/33 (12%) controls (P = .050). CRVO is associated with familial thrombophilia (factor V Leiden, factor VIII, low antithrombin III, homocysteinemia), and CRAO is associated with familial and acquired thrombophilia (low protein C, homocysteinemia, lupus anticoagulant), providing avenues for thromboprophylaxis, and triggering family screening.
Assuntos
Oclusão da Artéria Retiniana/etiologia , Oclusão da Veia Retiniana/etiologia , Adulto , Idoso , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/genética , Estudos de Casos e Controles , Fator V/genética , Feminino , Fibrinólise/genética , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/sangue , Complicações Cardiovasculares na Gravidez/genética , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/genética , Resultado da Gravidez , Estudos Prospectivos , Artéria Retiniana , Oclusão da Artéria Retiniana/sangue , Oclusão da Artéria Retiniana/genética , Oclusão da Veia Retiniana/sangue , Oclusão da Veia Retiniana/genética , Fatores de Risco , Trombofilia/sangue , Trombofilia/complicações , Trombofilia/genética , Trombose/sangue , Trombose/etiologia , Trombose/genéticaRESUMO
This article evaluates the prevalence of cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion. Forty-one patients with a first episode of a retinal artery occlusion underwent complete ophthalmic examination, routine blood testing and specific laboratory tests for thrombophilia, such as fasting and postmethionine homocysteine, lipoprotein(a), plasminogen activator inhibitor-1, factor VIII, factor V Leiden, factor II G20210A polymorphism, lupus anticoagulant and anticardiolipin antibodies. The control population consisted of 100 healthy individuals comparable as regards age and sex. At univariate analysis, hypertension, smoking, dyslipidaemia (both high cholesterol and triglyceride levels), antiphospholipid antibodies, hyperhomocysteinaemia, elevated factor VIII and lipoprotein(a) levels were significantly associated with retinal artery occlusion; at multivariate analysis, adjusted for age, sex, traditional and thrombophilic risk factors, smoking, hypercholesterolaemia, elevated homocysteine and lipoprotein(a) levels confirmed their independent role as risk factors for retinal artery occlusion. In conclusion, the results of the present pilot study demonstrate that the prevalence of hypercholesterolaemia and smoking and the 'thrombophilic burden' are increased in patients with retinal artery occlusion. Our findings may have implications for the management of these patients, suggesting the need for an intensive and tailored secondary prevention and new therapeutic approaches.
Assuntos
Doenças Cardiovasculares/complicações , Homocisteína/sangue , Hipercolesterolemia/complicações , Oclusão da Artéria Retiniana/complicações , Fumar/efeitos adversos , Trombofilia/complicações , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Estudos Transversais , Feminino , Humanos , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Projetos Piloto , Polimorfismo de Nucleotídeo Único/genética , Oclusão da Artéria Retiniana/genética , Fatores de Risco , Trombofilia/sangue , Trombofilia/genéticaRESUMO
We present a case in which mfERG and OCT helped to make a diagnosis of an old BRAO in the setting of compound heterozygous MTHFR genotype. A 44-year-old woman presented for evaluation of a 10 month history of persistently cloudy vision OS. She had been worked up previously for MS versus BRAO, and she was on coumadin, folate, and multivitamin at the time of presentation. The patient has a fraternal twin sister who was diagnosed with MS. Dilated fundus examination OS showed subtle inferior optic atrophy with slight narrowing of the inferotemporal retinal artery, and HVF test revealed a superonasal depression OS. mfERG also showed superonasal depression OS. Retinal origin of the chief complaint was further confirmed by OCT, which showed thinning of the NFL in the corresponding region of the retina OS. Coagulopathy evaluation revealed C677T/A1298C compound heterozygous genotype for MTHFR, and plasma homocysteine level after 6 months of folate and multivitamin supplementation was 10 microM (reference range 4-10 microM). The patient was diagnosed with BRAO and maintained on coumadin therapy.
Assuntos
Hiper-Homocisteinemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Oclusão da Artéria Retiniana/genética , Adulto , Eletrorretinografia , Feminino , Genótipo , Homocisteína/sangue , Humanos , Oclusão da Artéria Retiniana/diagnóstico , Tomografia de Coerência Óptica , Testes de Campo Visual , Campos VisuaisRESUMO
PURPOSE: An insertion/deletion (I/D) polymorphism of the gene for angiotensin-converting enzyme (ACE) is associated with higher ACE plasma levels and activity. This enzyme is known to play an important role in blood pressure regulation and the ACE I/D gene polymorphism has been suggested as a risk factor for atherosclerotic vascular diseases. The purpose of the present study was to investigate a hypothesized association between the ACE I/D polymorphism and retinal artery occlusion (RAO). METHODS: A total of 159 patients with RAO and 304 control subjects were enrolled in the present retrospective case-control study. ACE I/D genotypes were determined by polymerase chain reaction. RESULTS: Allelic frequencies and genotype distribution of the ACE I/D polymorphism did not significantly differ between patients and control subjects (ACE DD 25.8% versus 28.0%; p = 0.36). A logistic regression analysis predicted the presence of RAO by arterial hypertension and current smoking status, but not by ACE I/D genotypes. CONCLUSION: Our data suggest that the ACE I/D polymorphism is not a major risk factor for RAO.
Assuntos
Deleção de Genes , Mutagênese Insercional/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Oclusão da Artéria Retiniana/genética , Idoso , Estudos de Casos e Controles , DNA/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Hipertensão/genética , Masculino , Reação em Cadeia da Polimerase , Oclusão da Artéria Retiniana/enzimologia , Estudos Retrospectivos , Fatores de Risco , Fumar/genéticaRESUMO
BACKGROUND AND PURPOSE: Proinflammatory cytokines including interleukin-6 (IL-6) are supposed to play a pivotal role in the development of atherosclerosis. A common polymorphism in the promoter of the IL-6 gene (IL-6 -174G>C) affects plasma IL-6 concentrations and has been suggested as a risk factor for cardiovascular disease. The aim of the present case-control study was to investigate the role of this polymorphism for retinal artery occlusion (RAO). METHODS: One hundred eighty-two patients with RAO and 307 control subjects were genotyped for the IL-6 -174G>C polymorphism. Genotypes were determined by fluorogenic exonuclease (TaqMan) assay. RESULTS: The prevalence of the CC genotype was significantly lower in patients with RAO than in control subjects (10.4% versus 19.9%; P=0.006). Homozygosity for the C allele was associated with an odds ratio of 0.50 (95% CI, 0.28 to 0.89) for RAO. CONCLUSIONS: The CC genotype of the IL-6 -174G>C polymorphism may be associated with a protective effect against RAO.
Assuntos
Interleucina-6/genética , Polimorfismo Genético , Oclusão da Artéria Retiniana/genética , Idoso , Alelos , Pressão Sanguínea , Estudos de Casos e Controles , Complicações do Diabetes/genética , Feminino , Genótipo , Homozigoto , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Razão de Chances , Estudos RetrospectivosRESUMO
It is largely unknown to what extent genetic abnormalities contribute to the development of atherosclerotic renal artery disease. Among the potential candidate genes, those of the renin-angiotensin system and the endothelial nitric oxide synthase (eNOS) rank high because of their importance in the atherosclerotic process. We investigated the association of polymorphisms in these genes (the angiotensinogen Met235Thr, the angiotensin-converting enzyme insertion/deletion, the angiotensin II type-1 receptor A1166C, and the eNOS Glu298Asp) with the presence or absence of atherosclerotic renovascular disease in 456 consecutive hypertensive patients referred for renal angiography on the suspicion of renovascular hypertension. Nondiseased normotensive (n=200) and hypertensive (n=154) patients from a family practice served as external controls. Renal artery disease was present in 30% of our angiography group. The Asp allele of the eNOS Glu298Asp polymorphism was associated with atherosclerotic renal artery stenosis with an odds ratio of 1.44 (95% confidence interval 1.00 to 2.09) versus hypertensives with angiographically proven patent arteries, of 1.89 (1.24 to 2.87) versus hypertensive family practice controls, and of 2.09 (1.29 to 3.38) versus normotensive family practice controls. However, this allele also differed significantly between patients with patent renal arteries and normotensive and hypertensive controls. No differences were found with respect to the other genetic polymorphisms. We hypothesize that the Asp allele of the Glu298Asp polymorphism may predispose to the development of atherosclerotic lesions but that renal artery involvement depends on other factors, also.
Assuntos
Arteriosclerose/genética , Hipertensão Renovascular/genética , Óxido Nítrico Sintase/genética , Oclusão da Artéria Retiniana/genética , Idoso , Angiotensinogênio/genética , Arteriosclerose/diagnóstico por imagem , Feminino , Genótipo , Humanos , Hipertensão Renovascular/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Radiografia , Receptores de Angiotensina/genética , Oclusão da Artéria Retiniana/diagnóstico por imagem , Fatores de RiscoRESUMO
We report a case of sudden onset visual loss caused by branch retinal artery occlusion. Systematic search for the cause of branch retinal artery occlusion revealed Factor V Leiden mutation and antiphospholipid antibody syndrome as the cause. Implications for diagnosis and management are discussed.