IntroductionSickle cell disease (SCD) is an inflammatory condition with an increase in the adhesion of sickled erythrocytes, and it is a potential cause of vaso-occlusive episodes, an event related to clinical manifestations, morbidity and mortality. The cystathionine beta-synthase enzyme gene (CBS) and the methylenetetrahydrofolate reductase enzyme gene (MTHFR) are risk factors for thromboembolic disorders. This study evaluated the frequency of the 844ins68 CBS and C677T MTHFR gene polymorphisms and their possibility to be risk factors for vaso-occlusive crises.Material and methodsIn total 91 blood samples from SCD patients were studied by PCR-RFLP and PCR-allele-specific, for the SCD genotype confirmation and polymorphism identification.ResultsThe presence of clinical manifestations related to vaso-occlusive crises were more frequent among patients with the Hb SS genotype (p = 0.007). The CBS enzyme gene was three times more frequent (p = 0.011) among patients with vaso-occlusive complications. The MTHFR gene mutation frequency showed no increased risk for vaso-occlusive crises in SCD patients (p = 0.193). The interaction between the two polymorphisms was evaluated in 12.08% of the SCD patients and doubled the vaso-occlusive disease risk (relative risk: 2.16).ConclusionsWe conclude that the presence of 844ins68 CBS and C677T MTHFR gene polymorphism was a risk factor for vaso-occlusive episodes in the SCD patients evaluated.
A doença falciforme é uma condição inflamatória com fisiopatologia dependente de episódios vaso-oclusivos. Mutações nos genes metilenotetrahidrofolato redutase (MTHFR) e cistationinabeta-sintase (CBS), constituem fatores de risco para doenças vasculares. Diante da importância em se identificar fatores de risco para eventos vaso-oclusivos em doentes falciformes (DF), objetivamos avaliar a frequência das mutações C677T no gene MTHFR e 844ins68 no gene CBS nesses pacientes. Foram avaliados 300 individuos com HbSS, HbSC e HbS/Beta talassemia, provenientes de Brasília, Goiânia, Rio de Janeiro, São José do Rio Preto e São Paulo. Foram coletados 5mL de sangue venoso em EDTA, após consentimento informado. As metodologias clássicas foram realizadas para a confirmação do fenótipo de hemoglobina. As mutações para os genótipos de Hemoglobina e polimorfismos pesquisados foram avaliadas por Polimorfismo de Comprimento do Fragmento de Restrição e Alelo Específico. Os resultados mostraram que 93 pacientes (31,00%) foram heterozigotos e 13 (4,33%) homozigotos para a mutação C677T e 90 heterozigotos (30,00%) e 8 homozigotos (2,66%) para a mutação 844ins68, ambas com diferença significante para as frequências genotípicas entre para as localidades. As frequências alélicas estão em equilíbrio de Hardy-Weinberg para os dois polimorfismos. A frequência das mutações foi significativa e a presença de eventos vaso-oclusivos foi mais incidente nos pacientes com Hb SS (p=0007). A mutação 844ins68 foi aproximadamente três vezes mais frequente nos pacientes com presença de complicações vaso-oclusivas (p=0,011). A mutação C677T não mostrou associação com o risco para manifestações vaso-oclusivas (p=0, 193). A interação C677T/ 844ins68 ocorreu em 12,08% dos DF e mostrou aumento de duas vezes no risco para manifestação vaso-oclusiva. Assim concluímos que as frequências das mutações estão de acordo com o esperado para a população brasileira e que a presença da mutação 844ins68 no gene da CBS mostrou ser um potencial fator de risco para evento vaso-oclusivo nos DF avaliados Palavras-chave: Doença falciforme; vaso-oclusão; polimorfismos; MTHFR; CBS. AbstractSickle cell disease is an inflammatory condition with a pathophysiology that involves vaso-occlusive episodes. Mutations of the methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes are risk factors for vascular disease. Due to the importance of identifying risk factors for vaso-occlusive events in sickle cell patients, we investigated the frequencies of the C677T and 844ins68 mutations of the MTHFR and CBS genes, respectively. Three hundred patients with Hb SS, HB SC and HbS/Beta thalassemia, from Brasília, Goiânia, Rio de Janeiro, São Jose do Rio Preto and São Paulo were evaluated. Samples of 5 mL of venous blood were collected in EDTA after informed consent was received from patients. Classical diagnostic methods were used to confirm the hemoglobin phenotypes. The hemoglobin genotypes and polymorphisms studied were evaluated by Restriction Fragment Length Po...
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