Association between diet and polymorphisms in individuals with statin-controlled dyslipidaemia grouped according to oxidative stress biomarkers

Abstract

The objective of this study was to investigate whether differences in diet and in single-nucleotide polymorphisms (SNPs) found in paraoxonase-1 (PON-1), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) genes, are associated with oxidative stress biomarkers and consequently with susceptibility of low-density cholesterol (LDL) to oxidation. A multivariate approach was applied to a group of 55 patients according to three biomarkers: plasma antioxidant activity, malondialdehyde and oxidized LDL (oxLDL) concentrations. Individuals classified in Cluster III showed the worst prognoses in terms of antioxidant activity and oxidative status. Individuals classified in Cluster I presented the lowest oxidative status, while individuals grouped in Cluster II presented the highest levels of antioxidant activity. No difference in nutrient intake was observed among the clusters. Significantly higher γ-and δ-tocopherol concentrations were observed in those individuals with the highest levels of antioxidant activity. No single linear regression was statistically significant, suggesting that mutant alleles of the SNPs selected did not contribute to the differences observed in oxidative stress response. Although not statistically significant, the p value of the APO E coefficient for oxLDL response was 0.096, indicating that patients who carry the TT allele of the APO E gene tend to present lower plasma oxLDL concentrations. Therefore, the differences in oxidative stress levels observed in this study could not be attributed to diet or to the variant alleles of PON-1, CETP, HMGCR or APO E. This data supports the influence of γ-tocopherol and δ-tocopherol on antioxidant activity, and highlights the need for further studies investigating APO E alleles and LDL oxidation.Uniterms: Diet. Oxidative stress/biomarkers. Single-nucleotide polymorphism (SNPs). Lipoproteins/ oxidation. Statins. Apolipoprotein E.O objetivo deste estudo foi investigar se diferenças na dieta e em polimorfismos de nucleotídeos únicos (SNPs) encontrados no gene da paraoxonase 1 (PON-1), da 3-hidroxi-3-metilglutaril-coenzima A reductase (HMGCR), da proteína de transferência de ésteres de colesterol (CETP) e da apolipoproteina E (APOE) estariam associadas com biomarcadores do estresse oxidativo e, consequentemente, com a suscetibilidade da LDL à oxidação. Técnicas da estatística multivariada foram aplicadas a um grupo de 55 pacientes usando 3 biomarcadores: atividade antioxidante plasmática, concentrações de malondialdeído e LDL oxidada. Indivíduos classificados no cluster III apresentaram um prognóstico negativo em termos de atividade antioxidante e estado oxidativo. Os indivíduos agrupados no cluster I apresentaram o mais baixo nível de estado oxidativo, enquanto que indivíduos no cluster II apresentaram os mais altos níveis de atividade antioxidante. Nenhuma diferença na ingestão de nutrientes foi observada entre os clusters.Concentrações estatísticamente mais altas de γ-e δ-tocoferol foram...

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

“…CETP B2B2 genotype was shown to increase the HDL cholesterol after long term of simvastatin treatment (Fiegenbaum et al, 2005b). Whereas CETP Taq1B variant was not associated with differences in plasma tocopherol and oxidative stress biomarkers, such as malondialdehyde, oxidized LDL and total antioxidant activity, in a study with HC subjects treated with simvastatin or atorvastatin (Botelho et al, 2012).…”

“…Carriers of PON1 192Arg and 55Met alleles are more likely of achieving HDL cholesterol goals after long term treatment with simvastatin and atorvastatin (OR: 2.81, CI95%:1.35-5.85, P =0.006) (De Souza et al, 2015). On the other hand PON1 Gln192Arg was not associated with differences in plasma tocopherol and oxidative stress biomarkers, in HC subjects treated with simvastatin or atorvastatin for six months (Botelho et al, 2012).…”

“…Interestingly, APOE *3*3 genotype carriers had greater reduction of APOE mRNA levels in PBMC after atorvastatin treatment (Issa et al, 2012). Another study investigated the APOE g.4798T>G in subjects with statin-controlled dyslipidemia and did not find association with oxidative stress biomarkers and plasma tocopherol (Botelho et al, 2012).…”

“…One study investigated the HMGCR SNP29 in Brazilian HC patients taking long term treatment with simvastatin or atorvastatin (10-80 mg/day), but no association was found with oxidative stress biomarkers, such as plasma malondialdehyde, oxidized LDL and total antioxidant activity, and plasma tocopherol (Botelho et al, 2012).…”