Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Atherosclerosis/therapy , Cholesterol/blood , Dyslipidemias/therapy , Atherosclerosis/prevention & control , Biomarkers/blood , Cardiovascular Diseases/etiology , Cholesterol Esters/blood , Dyslipidemias/blood , Dyslipidemias/prevention & control , Fatty Acids/metabolism , Fibric Acids/metabolism , Hypercholesterolemia/blood , Hypertriglyceridemia/blood , Life Expectancy , Lipoproteins/metabolism , Risk Factors , Triglycerides/bloodABSTRACT
The MDR1 gene encodes the P-glycoprotein, an efflux transporter with broad substrate specificity. P-glycoprotein has raised great interest in pharmacogenetics because it transports a variety of structurally divergent drugs, including lipid-lowering drugs. The synonymous single-nucleotide polymorphism C3435T and the nonsynonymous single-nucleotide polymorphism G2677T/A in MDR1 have been indicated as potential determinants of variability in drug disposition and efficacy. In order to evaluate the effect of G2677T/A and C3435T MDR1 polymorphisms on serum levels of lipids before and after atorvastatin administration, 69 unrelated hypercholesterolemic individuals from São Paulo city, Brazil, were selected and treated with 10 mg atorvastatin orally once daily for four weeks. MDR1 polymorphisms were analyzed by PCR-RFLP. C3435T and G2677T polymorphisms were found to be linked. The allelic frequencies for C3435T polymorphism were 0.536 and 0.464 for the 3435C and 3435T alleles, respectively, while for G2677T/A polymorphism allele frequencies were 0.580 for the 2677G allele, 0.384 for the 2677T allele and 0.036 for the 2677A allele. There was no significant relation between atorvastatin response and MDR1 polymorphisms (repeated measures ANOVA; P > 0.05). However, haplotype analysis revealed an association between T/T carriers and higher basal serum total (TC) and LDL cholesterol levels (TC: 303 ± 56, LDL-C: 216 ± 57 mg/dl, respectively) compared with non-T/T carriers (TC: 278 ± 28, LDL-C: 189 ± 24 mg/dl; repeated measures ANOVA/Tukey test; P < 0.05). These data indicate that MDR1 polymorphism may have an important contribution to the control of basal serum cholesterol levels in Brazilian hypercholesterolemic individuals of European descent.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Cholesterol, LDL/blood , Genes, MDR/genetics , Haplotypes/genetics , Hypercholesterolemia/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Anticholesteremic Agents/therapeutic use , Brazil , Cholesterol, LDL/genetics , White People , Gene Frequency , Heptanoic Acids/therapeutic use , Hypercholesterolemia/blood , Hypercholesterolemia/drug therapy , Hypercholesterolemia/ethnology , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Pyrroles/therapeutic useABSTRACT
Etudos têm demonstrado que o sedentarismo está associado com maior incidência de doença coronária. Inversamente, a prática regular de atividade física é útil na prevençäo primária e secundária dessa importante doença. Os mecanismos pelos quais os exercícios físicos influem sobre a doença coronária näo estäo total totalmente elucidados. Sabe-se que a açäo benéfica da atividade física pode depender da melhora da capacidade cardiorrespiratória e da atuaçäo sobre vários fatores de risco importantes paro desencadeamento da aterosclerose coronária. Tem sido demonstrado que a intensidade de exercício capas de melhorar o perfil metabólico é menor do que a necessária para levar o incremento importante da capacidade cardiorrespiratória.