RESUMO
BACKGROUND: The present study was designed to investigate the effects of apoB XbaI and apoA-I/C-III/A-IV SstI polymorphisms to carotid artery intima-media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow-mediated vasodilatation (FMD). METHODS AND RESULTS: As part of the Cardiovascular Risk in Young Finns Study, the carotid IMT, CAC and brachial FMD of 2,265 subjects (mean age +/- SD 32 +/-5 years) were measured with ultrasonography, and genotyping of the apolipoprotein polymorphisms was performed. The frequencies of the genotypes did not differ between the groups with high (above median 0.57 mm) and low (below median) IMT, CAC or FMD. The average carotid IMT differed between the 3 apoB XbaI genotypes (ANOVA, p=0.04), but not between the apoA-I/C-III/A-IV SstI genotypes (ANOVA, p=0.53). The relationship between the polymorphisms and carotid IMT was not significant in any of the covariate-adjusted logistic and linear regression analyses. CAC and FMD were not influenced by either of the polymorphisms in ANOVA and regression analyses. CONCLUSIONS: The polymorphisms apoA-I/C-III/A-IV SstI and apoB XbaI do not seem to affect carotid artery characteristics or brachial artery FMD in young adulthood.
Assuntos
Apolipoproteínas/genética , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Polimorfismo Genético , Adolescente , Adulto , Análise de Variância , Apolipoproteína A-I/genética , Apolipoproteína C-III/genética , Apolipoproteínas A/genética , Apolipoproteínas B/genética , Aterosclerose/genética , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Criança , Pré-Escolar , Complacência (Medida de Distensibilidade) , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Fluxo Sanguíneo Regional , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia , VasodilataçãoRESUMO
BACKGROUND: Apolipoprotein E (ApoE) is known to modulate lipoprotein transport and metabolism. The common APOE epsilon2/epsilon3/epsilon4 polymorphism explains part of the variation in plasma cholesterol levels. Polymorphisms of the APOE gene regulatory region are suggested to be involved in explaining variation of lipoprotein levels within the APOE epsilon2/epsilon3/epsilon4 genotypes. OBJECTIVES: To study the associations of the APOE gene promoter polymorphisms -219G/T and +113G/C and their haplotypes with serum lipid and lipoprotein concentrations, especially within the most common APOE epsilon3/epsilon3 genotype group. SUBJECTS AND METHODS: From 219 middle-aged Finnish men, APOE genotypes were determined and haplotypes estimated. Plasma lipoproteins were isolated by ultracentrifugation and their lipids were measured. RESULTS: The studied APOE promoter polymorphisms and haplotypes associated with certain lipid variables independently of the APOE epsilon2/epsilon3/epsilon4 genotype. Within the APOE epsilon3/epsilon3 group, both -219G/G and +113G/G genotypes associated statistically significantly with higher levels of very low-density lipoprotein (VLDL) cholesterol, apoB and triglycerides, and tended to associate with lower HDL-cholesterol concentrations than the other genotypes. Compared with the -219T/+113C/epsilon3 haplotype, the more common -219G/+113G/epsilon3 haplotype was found more frequently among the group having high (over median) VLDL-cholesterol and triglyceride concentrations (OR 2.6, p<0.001 and OR=2.1, p=0.009, respectively). CONCLUSIONS: In addition to the APOE epsilon2/epsilon3/epsilon4 polymorphism, the promoter polymorphisms -219G/T and +113G/C as well as their haplotype modulate lipid and lipoprotein concentrations in middle-aged Finnish men.