Fundamentos:Evidências sugerem que a paroxonase 1 (PON1) confere importantes propriedades antioxidantes e antiinflamatórias quando associada à lipoproteína de alta densidade (HDL).Objetivo:Investigar as relações entre o SNP p.Q192R da PON1, parâmetros bioquímicos e aterosclerose carotídea em uma amostra populacional brasileira assintomática e normolipidêmica.Métodos:Foram estudados 584 voluntários (mulheres, n = 326; homens, n = 258; idade entre 19-75 anos). Foi extraído DNA genômico total e o SNP foi detectado na plataforma de genotipagem TaqMan® SNP OpenArray®(Applied Biosystems, Foster City, CA). Foram dosadas lipoproteínas e apolipoproteínas plasmáticas, e a atividade da PON1 foi medida utilizando-se paraoxon como substrato. Foi utilizada ultrassonografia bidimensional de alta resolução para determinar a espessura íntimo‑medial das artérias carótidas (EIMc) e a presença de placas ateroscleróticas carotídeas em um subgrupo de indivíduos (n = 317).Resultados:A presença de p.192Q esteve associada a um aumento significativo da atividade da PON1 (RR = 12,30 (11,38); RQ = 46,96 (22,35); QQ = 85,35 (24.83) μmol/min; p < 0,0001), HDL-C (RR = 45 (37); RQ = 62 (39); QQ= 69 (29) mg/dL; p < 0,001) e apo A-1 (RR = 140,76 ± 36,39; RQ = 147,62 ± 36,92; QQ = 147,49 ± 36,65 mg/dL; p = 0,019). A análise de regressãostepwise mostrou que heterozigotos e portadores de p.192Q influenciaram 58% da atividade da PON1 em relação ao paraoxon. A análise de regressão linear univariada demonstrou que não houve associação entre o SNP p.Q192R e a EIMc média; como resultado, na análise de regressão múltipla nenhuma variável foi selecionada com 5% de significância. Os parâmetros estudados não se associaram à presença de placas carotídeas na análise de regressão logística.Conclusão:Em indivíduos de baixo risco, a presença da variante p.192Q daPON1 mostrou-se associada a um perfil lipídico plasmático benéfico e à ausência de aterosclerose de carótida.

Background:Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL).Objective:To investigate the relationships between p.Q192R SNP ofPON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.Methods:We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317).Results:The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques.Conclusion:In low-risk individuals, the presence of the p.192Q variant ofPON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

Glycogen storage disease (GSD) comprises a group of autosomal recessive disorders characterized by deficiency of the enzymes that regulate the synthesis or degradation of glycogen. Types Ia and Ib are the most prevalent; while the former is caused by deficiency of glucose-6-phosphatase (G6Pase), the latter is associated with impaired glucose-6-phosphate transporter, where the catalytic unit of G6Pase is located. Over 85 mutations have been reported since the cloning of G6PC and SLC37A4 genes. In this study, twelve unrelated patients with clinical symptoms suggestive of GSDIa and Ib were investigated by using genetic sequencing of G6PC and SLC37A4 genes, being three confirmed as having GSD Ia, and two with GSD Ib. In seven of these patients no mutations were detected in any of the genes. Five changes were detected in G6PC, including three known point mutations (p.G68R, p.R83C and p.Q347X) and two neutral mutations (c.432G > A and c.1176T > C). Four changes were found in SLC37A4: a known point mutation (p.G149E), a novel frameshift insertion (c.1338_1339insT), and two neutral mutations (c.1287G > A and c.1076-28C > T). The frequency of mutations in our population was similar to that observed in the literature, in which the mutation p.R83C is also the most frequent one. Analysis of both genes should be considered in the investigation of this condition. An alternative explanation to the negative results in this molecular study is the possibility of a misdiagnosis. Even with a careful evaluation based on laboratory and clinical findings, overlap with other types of GSD is possible, and further molecular studies should be indicated.