Avalia??o dos polimorfismos e express?o do RNAm do TREML4 em leuc?citos de pacientes com doen?a arterial

• Main Author: Duarte, Victor Hugo Rezende
• Other Authors: 32160245801
• Language: Portuguese
• Published: PROGRAMA DE P?S-GRADUA??O EM CI?NCIAS FARMAC?UTICAS 2017
• Subjects: CNPQ::CIENCIAS DA SAUDE::FARMACIA; Doen?a cardiovascular; Extens?o da les?o coronariana; TREML4; Polimorfismos; Express?o de RNAm; ?ndice de Friesinger
• Online Access: https://repositorio.ufrn.br/jspui/handle/123456789/23420

Submitted by Automa??o e Estat?stica ([e-mail]) on 2017-06-02T21:45:30Z No. of bitstreams: 1 VictorHugoRezendeDuarte_DISSERT.pdf: 944081 bytes, checksum: b102ccdae8dc58e29f3c26819c75b9c6 (MD5) === Approved for entry into archive by Arlan Eloi Leite Silva ([e-mail]) on 2017-06-07T21:07:26Z (GMT) No. of bitstreams: 1 VictorHugoRezendeDuarte_DISSERT.pdf: 944081 bytes, checksum: b102ccdae8dc58e29f3c26819c75b9c6 (MD5) === Made available in DSpace on 2017-06-07T21:07:26Z (GMT). No. of bitstreams: 1 VictorHugoRezendeDuarte_DISSERT.pdf: 944081 bytes, checksum: b102ccdae8dc58e29f3c26819c75b9c6 (MD5) Previous issue date: 2017-04-26 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) === As prote?nas da fam?lia triggering receptor expressed on myeloid cells (TREM) s?o associados com o risco e progress?o da aterosclerose. Em resultados pr?vios observamos que a alta express?o do TREML4est? relacionada com fase inicial da S?ndrome Coronariana Aguda (SCA).Neste estudo, investigamos a rela??o dos polimorfismos e a express?o do RNAm do TREML4 em leuc?citos de pacientes estratificados de acordo com a extens?o das les?es das atr?rias coron?rias. Foram inclu?dos pacientes com doen?a arterial coronariana (DAC) (n=151), com idades entre 30 e 74 anos, submetidos ? angiografia coron?ria eletiva. A extens?o da les?o coronariana foi avaliada atrav?s do ?ndice de Friesinger. Os polimorfismosrs2803495 (A> G), rs2803496 (T> C) e aexpress?o do RNAm do TREML4 em leuc?citos foram analisadas por qRT-PCR. A express?o de TREML4 foi maior em pacientes com les?es coronarianas graves em rela??o aos sem les?o, baixas e intermedi?rias, (p <0.05). Indiv?duos portadores do alelo G do rs2803495 (gen?tipos AG / GG) e do alelo C do rs2803496(gen?tipos TC / CC) apresentaram uma express?o de RNAm de TREML4 positiva (Alelo G: OR = 2.4, 95% CI 1.0-5.7, p < 0.05; e Alelo C: OR = 7.8, 95% CI = 2.9-20.9, p < 0.01, respectivamente).Entretanto, os polimorfismos do TREML4 n?o foram associados com as extens?es das les?es coron?rias. Em conclus?o, a express?o aumentada de mRNA de TREML4 nos leuc?citos ? influenciada por polimorfismos e est? associada a les?es mais graves das art?rias coron?rias, sugerindo seu papel como potencial biomarcador para investigar a extens?o da les?o coronariana em pacientes com DAC. === The members of the triggering receptor expressed on myeloid cells (TREM) family are associated with the risk and progression of atherosclerosis. We previously reported the upregulation of TREML4 in the early phase of theacute coronary syndrome. Here, we investigated the relationship of TREML4 polymorphisms and mRNA expression in blood leukocytes of patients stratificate accordingto the extension of coronary artery lesion. Patients with coronary artery disease (CAD) (n = 151), aged 30 to 74 years and undergoing elective coronary angiography,were selected. The extension of coronary lesion was assessed by the Friesinger index.TREML4 rs2803495 (A>G) and rs2803496 (T>C) variants andleukocyte mRNA expression were analyzed by qRT-PCR. TREML4 expression was higher in patients with major coronary artery lesions compared to subjects without or with low and intermediate lesions, (p < 0.05). Subjects carrying rs2803495 G allele (AG/GG genotypes) and rs2803496 C allele (TC/CC genotypes) were more prone to have positive TREML4 mRNA expression (Allele G: OR = 2.4, 95% CI 1.0-5.7, p < 0.05; allele C: OR = 7.8, and 95% CI = 2.9-20.9, p < 0.01, respectively).However, TREML4 polymorphisms were not associated with the extent of coronary lesion.In conclusion, increased TREML4 mRNA expression in blood leukocytes is influenced by gene polymorphisms and it is associated with more severe coronary artery lesions, suggesting its role as potential biomarker to investigate the extent of coronary lesion in CAD patients.