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Master's Dissertation
DOI
10.11606/D.5.2012.tde-11052012-113317
Document
Author
Full name
Karolline Santana da Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Bydlowski, Sergio Paulo (President)
Morgante, Angela Maria Vianna
Pereira, Juliana
Title in Portuguese
Estudo dos polimorfismos nos genes das paraoxonases 1 e 2 em pacientes com linfoma difuso de grandes células B
Keywords in Portuguese
Enzimas
Linfoma difuso de grandes células B
Paraoxonases
Polimorfismos genéticos
Abstract in Portuguese
A família paraoxonase (PON1, PON2 e PON3) tem sido objeto de grande interesse por prevenir o estresse oxidativo e o processo inflamatório, condições importantes na carcinogênese. O Linfoma Difuso de Grandes Células B (LDGCB) consiste no subtipo histológico mais comum dentre os linfomas, doenças que se originam a partir das células do tecido linfoide e exibem distintos comportamentos clínicos, fatores patológicos e características epidemiológicas. Há escassez de dados sobre a atuação das paraoxonases na susceptibilidade diferencial ao risco de linfomas. Deste modo, o objetivo do presente estudo foi investigar a frequência alélica e genotípica dos polimorfismos 192QR e 55LM, no gene da PON1, e 148AG e 311SC, no gene da PON2 e o efeito desses polimorfismos sobre as atividades da enzima PON e perfil lipídico em 182 indivíduos (78 pacientes com LDGCB e 104 indivíduos saudáveis). O sangue foi coletado, em 4 momentos, para a determinação do perfil lipídico e das atividades arilesterase e paraoxonase da PON. O DNA foi extraído de leucócitos do sangue periférico pelo método de extração salina. A análise dos polimorfismos foi realizada por PCR/RFLP. Não houve diferença estatística na distribuição de genótipos e frequência de alelos dos polimorfismos nos genes da PON1 e PON2. A atividade sérica da arilesterase apresentou valores significativamente maiores apenas entre os indivíduos saudáveis (p=0,001). As variantes 55MM e 192QQ, do gene da PON1, influenciaram as atividades arilesterase (p=0,011) e paraoxonase (0,001). O polimorfismo PON2 311SS associou-se a atividade arilesterase (p=0,021). A concentração de autoanticorpos oxLDL foi alterada, pela presença do genótipo 55LM (p=0,037) nos indivíduos com LDGCB
Title in English
Study of polymorphisms in the paraoxonase 1 and 2 genes in patients with diffuse large B cell lymphoma
Keywords in English
Diffuse large B Cell
Enzyme
Genetics polymorphisms
Paraoxonase
Abstract in English
The paraoxonase family (PON1, PON2 and PON3) have been the subject of great interest, since they are responsible for preventing oxidative stress and inflammation, conditions important in carcinogenesis. The Diffuse Large B Cell Lymphoma (DLBCL) is the most common histological subtype among lymphomas, diseases that originate from cells of the lymphoid tissue and exhibit clinically distinct behaviors and pathological and epidemiological factors. There are paucity of data on the activity of paraoxonase in the differential susceptibility to the risk of lymphoma. Thus, the objective of this study was to investigate the genotypic and allelic frequency of polymorphisms 192QR and 55LM, in the PON1 gene and 148AG and 311SC, in the PON2 gene and the effect of these polymorphisms on PON enzyme activities and lipid profile in 182 subjects (78 patients with DLBCL and 104 healthy subjects). Blood was collected in four moments for the determination of lipid profile and paraoxonase and arylesterase activities of PON. The DNA was extracted from peripheral blood leukocytes by salt extraction method. The analysis of polymorphisms was performed by PCR/RFLP. There was no statistical difference in the distribution of genotypes and allele frequencies of polymorphisms in the PON1 and PON2 genes. The serum arylesterase activity was significantly higher only among healthy subjects (p=0.001). 192QQ and 55MM variants of the PON1 gene, influenced arylesterase (p=0.011) and paraoxonase (0.001) activities. The PON2 polymorphism was associated with 311SS arylesterase activity (p = 0.021). The concentration of oxLDL autoantibodies was altered by the presence of 55LM genotype (p = 0.037) in patients with DLBCL
 
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Publishing Date
2012-05-15
 
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