Análise dos polimorfismos dos genes CP, CYBRD1, HAMP e SLC40A1 nos pacientes com porfiria cutânea tardia

• Autor(a) principal: Succi, Isabella Brasil
• Data de Publicação: 2017
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/8537
• topic: Porphyria cutanea tarda; Genomics; Population Characteristics; Porfiria cutânea tardia; Genética; Características da População; Dermatologia; Porfiria cutânea tardia; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DERMATOLOGIA

Porphyria cutanea tarda (PCT) is the most common type of porphyria and of greatest dermatological interest. It occurs due to deficiency of uroporphyrinogen decarboxylase (UROD) activity. Its etiology is not completely understood, clinical expression depends on both genetic and acquired factors. Iron overload has been commonly found in PCT patients. The exact reason why the iron accumulates in these patients is unknown. There is increasing evidence that hepatic siderosis is the critical point in PCT pathogenesis. We aimed to evaluate the role of polymorphisms in CP, CYBRD1, HAMP and SLC40A1 genes that affects iron homeostasis in PCT patients. Because the Brazilian population is heterogeneous (with African and Amerindian contributions), we also investigate the genetic ancestry of these patients. The 30 patients from Rio de Janeiro included in the study had been diagnosed with sporadic PCT based on clinical and laboratory results. Analysis of the genetic ancestry of PCT patients were obtained through 46 ancestry informative markers - INDELS. Alleles were discriminated using the ABI StepOnePlus Real-Time PCR System using TaqMan Assays, according to the manufacturer s instructions. The results obtained through genetic ancestry revealed prevalent European ancestry (70.2%). African and Amerindian ethnicities were less common: 20.1% and 9.7%, respectively. Our Statistical analysis revealed no relationships among genotype, allele frequency, and genetic ancestry. The G allele of the CP gene was more common among patients. The frequencies of the GG and AG genotypes were higher in the PCT group than in healthy individuals. We also found higher frequencies of the C allele of SLC40A1 in controls compared with PCT patients. The CC and CT genotypes were more frequent in healthy individuals. Our data highlight a possible role for the CP gene in predicting PCT. The present analysis shows a higher frequency of the G variant in these patients. Regarding the SLC40A1, the presence of a C allele could protect against iron overload. A single C allele might be sufficient to protect against the disease.