Associação entre variações alélicas clássicas do gene da ApoE com fatores de risco cardiovascular em indivíduos muito idosos

Monografia (graduação)—Universidade de Brasília, Faculdade de Ceilândia, Curso de Farmácia, 2013.Introdução: Levantamentos epidemiológicos indicam a influência de polimorfismos da ApoE sobre níveis plasmáticos de lipídeos e lipoproteínas ricas em triglicerídeos, com impactos sobre fenótipos ateroscleróticos. Objetivo: Estudar a associação dos genótipos clássicos do gene da ApoE com fatores de risco clínicos e bioquímicos para a aterosclerose em um segmento muito idoso da população brasileira, com destaque para o perfil lipêmico. Métodos: Foram realizadas avaliações transversais de parâmetros clínicos e laboratoriais, incluindo tomografia cardíaca computadorizada, dos 208 participantes com base nos alelos ε2, ε3 e ε4 do gene da ApoE. Resultados: Quando foram comparados os não-carreadores do alelo ε4 com os carreadores, níveis plasmáticos mais baixos de ApoB, assim como da razão ApoB/ApoA foram observados no primeiro grupo. A avaliação do polimorfismo da ApoE com outras variáveis e com a calcificação arterial não apresentaram diferenças significativas entre os grupos. Conclusão: O estudo sugere que o papel aterogênico do alelo ε4 pode, pelo menos em parte, ser atribuído a um aumento na razão ApoB/ApoA, devido aos altos níveis de ApoB em carreadores ε4 em comparação aos não-portadores. _________________________________________________________________________ ABSTRACTBackground: Epidemiological surveys indicate the influence of polymorphisms of the Apolipoprotein (Apo) E on plasma lipids and triglyceride-rich lipoprotein levels, with impact on atherosclerotic phenotypes. Objective: To study the association of classic genotypes of the ApoE gene with clinical and biochemical risk factors for atherosclerosis in a segment of the very old Brazilian individuals, with emphasis to the lipemic profile. Methods: We performed cross-sectional analyses of clinical and laboratory assessments, including cardiac computed tomography, across ε2, ε3 and ε4 carriers of the ApoE gene in 208 participants eligible for primary prevention. Results: When non-ε4 carries were compared with ε4 carrying subjects, lower levels of ApoB as well as on the ApoB/ApoA ratio were observed in the former group. Tests between ApoE polymorphisms with other variables and with arterial calcification showed no significant differences between groups. Conclusion: The study suggests that the atherogenic role of ε4 allele can at least in part be attributed to an increased ApoB/ApoA ratio due to higher levels of ApoB in ε4 carriers compared to non-carriers

Evidence for a contribution of the APOE (but not the ACE) gene to the sleep profile of non-demented elderly adults

This study aims to investigate alleles of the human apolipoprotein E (APOE) and of the angiotensin-converting enzyme (ACE) genes as risk factors for poor quality of sleep in elderly individuals with no major cognitive decline. This cross-sectional, analytical study was conducted with 163 participants aged 75 years in average and 85% female. Sociodemographic, anthropometric and clinical data were gathered, and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth scale, with patient followed for years prior to these evaluations to rule out onset of major mental disorders. Genotyping of classic polymorphic sites for the ApoE (rs429358 and rs7412) and the ACE (rs4646994) genes used peripheral DNA. A total of 63% of the subjects reported poor quality of sleep assessed by the PSQI whereas 54 (33%) reported daytime sleepiness through the Epworth scale. A significant correlation was observed between APOE and PSQI, with a greater frequency of the poor nighttime sleep quality phenotype among ε2 carriers, whereas no correlation was found among any of the sleep scores and the ACE genotypes. Thus, we suggest a correlation between APOE alleles and scale-assessed sleep quality scores in older adults, with no implications for ACE alleles, in a context devoid of cognitive impairment

Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer

Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence