Estudo dos genes modificadores da doença poliquística renal associados à doença cardiovascular

Tese de mestrado, Biologia Humana e Ambiente, Universidade de Lisboa, Faculdade de Ciências, 2015 ; The autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of cysts in the kidneys, which can progress to end-stage renal disease (ESRD). The genes of MTHFR, the CβS and GST are involved in the homocysteine cycle, cardiovascular risk marker. Hp, is an acute phase protein, associated to innate immunity, with antioxidant and anti-inflammatory properties. The purpose is to study the progression of ADPKD to ESRD taking into account the modulation of genetic polymorphisms of MTHFR, CBS, Hp, and GSTT1 and GSTM1 genotype-phenotype, biochemical relationship. The sample consisted of 883 subjects (N = 150 ADPKD, N = 144 DMII, N = 95 DMII-DRC, N = 94 N = DRT and 495 controls). The progression of CKD was evaluated according to the Cockcroft-Gault equation or creatinine in the urine. Genetic polymorphisms were determined by PCR and PCR-RFP. The phenotype of Hp was determined by electrophoresis on polyacrylamide gel. Creatinine, iron and ferritin in plasma were determined by standard methods. The erythrocyte activities: transmembrane reductase (TMR), methemoglobin reductase and acid phosphatase (AP) were determined by spectrophotometry. Statistical analysis was performed using SPSS 21.0 program. Statistically significant values for p <0.05. The GSTM1 null genotype was associated with risk for ADPKD compared to controls. The CT MTHFR genotype was protective for ADPKD and CKD. In rapid progressors, 2.1 Hp phenotype and genotype GSTM1 null were protective and not null genotype was associated with risk. In genotype-phenotype-biochemical relationship, AP was lower in DMII in relation to all groups; in ADPKD, the RTM was higher compared to ESRD or CKD-DMII. The polymorphisms analyzed may influence the progression of ADPKD for CKD. The activity of erythrocyte enzymes seem to be related to the etiology of the disorders studied reflecting the variation of erythropoietin, homocysteine and increased ...