FARMACOGENÉTICA DE FÁRMACOS HIPOLIPEMIANTES

Although, the pharmacological treatment for cholesterol reduction has been an advance in the cardiovascular and atherosclerosis treatment, the benefits are still limited due to interindividual variability in the response to these drugs. Disease severity, treatment adhesion, physiological conditions, biological conditions as well as the patient genetic profile could be cited as important factors for the evaluation of interindividual variability. In this context, three large groups of genes could be investigated: a) Genes that codify proteins involved in metabolism and/or transport of drugs, influencing the pharmacokinetics of these compounds. b) Genes that codify proteins involved in the mechanism of action and/or in the metabolic pathway where of drug action (pharmacodynamics). c) Genes that codify proteins involved in the direct development of the disease or in intermediate phenotypes. In this revision we discussed pharmacogenetic studies of the main lipid lowering drugs, and the expectations in relation to pharmacogenetics in order to help our prediction capacity in relation to treatment efficacy as well as the possibility to reduce adverse effects of these drugs. As soon as new studies would be performed and that most of the genetic variability associated with drug action would be disclosed, the great challenge would be the application of this knowledge in practical medicine.Embora o tratamento farmacoterapêutico para redução dos níveis de colesterol tenha sido um dos grandes avanços no tratamento de doenças cardiovasculares e aterosclerose, os benefícios são ainda limitados devido a variabilidade interindividual na resposta a esses medicamentos. Entre os fatores importantes para a avaliação da variabilidade interindividual pode-se citar a severidade da doença, adesão ao tratamento, condições fisiológicas, condições biológicas e o perfil genético do paciente. Neste contexto, três grandes grupos de genes podem ser analisados: a) Genes que codificam proteínas envolvidas na metabolização e/ou transporte dos fármacos, influenciando a farmacocinética dos compostos. b) Genes que codificam proteínas envolvidas no mecanismo de ação e/ou nas rotas metabólicas em que o fármaco age (farmacodinâmica). c) Genes que codificam proteínas envolvidas no desenvolvimento direto da doença ou de fenótipos intermediários. Nessa revisão discutimos os estudos farmacogenéticos dos principais fármacos hipolipemiantes e a expectativa em relação a fármacogenética de auxiliar em nossa capacidade de predição em relação à eficácia do tratamento e a possibilidade de redução dos efeitos adversos a esses medicamentos. Na medida que novos estudos forem efetuados e que a grande parte da variabilidade genética envolvidas nas diferenças interindividuais na ação de fármacos for elucidada, o grande desafio será a aplicação desses conhecimentos na prática médica

Diversity of two short tandem repeat loci (CD4 and F13A1) in three Brazilian ethnic groups

Two microsatellites (CD4 and F13A1) were investigated in seven Brazilian populations: one group each of European- and African-derived subjects from Porto Alegre, southern Brazil, and five Amerindian tribes (three Tupi-Monde speaking [Gaviao, Surui, and Zoro], one Macro-Ge [Xavante], and one Carib [Wai-Wai]). For both markers, neo-Brazilians presented with a high diversity, but Amerindians showed a low level of variability. Genotype frequency distributions were heterogeneous among populations, the only exception being similar CD4 frequencies in Afro- and Euro-Brazilians. Gene diversity analysis revealed that most of the total variation is due to intrapopulational diversity in all populations, Because of the high information content of these markers in Afro- and Euro-Brazilians, these systems are most appropriate for forensic analyses. The comparison among Brazilian and other world populations revealed high similarity among populations of the same ethnic group, indicating a high discriminative power for these markers

Apolipoprotein E Polymorphism and Its Association with Serum Lipid Levels in Brazilian Children

The influence of apolipoprotein E (APOE) genotypes on plasma lipid levels was determined in 414 Brazilian healthy children of mixed ethnicity, age 5 to 15 years (mean 8.9 2.9). The APOE*3 allele was the most frequent (77%), followed by APOE*4 (17%) and APOE*2 (6%). The pattern of lipid differences among genotypes was similar in both boys and girls. We did not detect an increase in cholesterol levels with the presence of the APOE*4 allele. Because a growing body of evidence suggests that the effect of *4 depends on its interaction with diet, the frequency of *4 might be more variable in children than in adults as well as among populations. Children carrying a *2 allele had lower total cholesterol (TC) and LDL-cholesterol levels (138.47 24.32 and 77.72 19.42, respectively) compared with *3/*3 children (158.33 25.28 and 97.05 21.82, respectively). Mean TC/HDLC ratio was also lower in children with the APOE*2 allele (3.27 0.66 versus 3.64 0.76). In this highly admixed population sample, the *2 anti-atherogenic lipid pattern is already detected in children

Cannabinoid Type-1 Receptor Gene Polymorphisms Are Associated with Central Obesity in a Southern Brazilian Population

The CB1 cannabinoid receptor and its endogenous ligands, the endocannabinoids, are involved in energy balance control, stimulating appetite and increasing body weight in wasting syndromes. Different studies have investigated the relationship between polymorphisms of the cannabinoid receptor 1 (CNR1) gene and obesity with conflicting results. In the present study, we investigated the 1359G/A (rs1049353), 3813A/G (rs12720071) and 4895A/G (rs806368) polymorphisms in the CNR1 gene in a Brazilian population of European descent. To verify the association between these variants and obesity-related traits in this population, 756 individuals were genotyped by PCR-RFLP methods. The 4895G allele was associated with waist to hip ratio (WHR) (P = 0.014; P = 0.042 after Bonferroni correction). An additive effect with the GAA haplotype was associated with WHR (P = 0.028), although this statistical significance disappeared after Bonferroni correction (P = 0.084). No significant association was observed between the genotypes of the 1359G/A and 3813A/G polymorphisms and any of the quantitative variables investigated. Our findings suggest that CNR1 gene polymorphism is associated with central obesity in this Brazilian population of European ancestry