RESUMO
Apolipoproteins have an important role in lipid metabolism and transport. Polymorphisms in the APOA1/C3/A4/A5 gene cluster have been associated with lipid alterations and cardiovascular diseases. We investigated APOA1 XmnI, APOA5 S19W, and APOA5 -1131T>C polymorphisms in 377 individuals from a cohort of a longitudinal Brazilian elderly study. Allele frequencies, genotype distribution, and association with major morbidities as well as with lipids, creatinine, albumin, urea, glycated hemoglobin, and fasting glucose serum levels were investigated. Linkage disequilibrium and haplotype associations were also analyzed. This is the first time that haplotypes involving these polymorphisms were evaluated. Genotyping was performed by PCR-RFLP. Minor allele frequencies were 0.119, 0.071, and 0.158 for XmnI, S19W, and -1131T>C polymorphisms, respectively. We found a significant association of the -1131C allele with low LDL-C levels. We also observed that XmnI and S19W polymorphisms were in linkage disequilibrium. The C/G haplotype, which is composed of the wild-type allele of XmnI and the minor allele of S19W, was associated with high total cholesterol serum levels in this elderly population. We conclude that the -1131T>C polymorphism and the C/G haplotype, including XmnI and S19W polymorphisms, are associated with alterations in lipid levels and may be risk factors for cardiovascular disease in the Brazilian elderly.
Assuntos
Apolipoproteína A-I/genética , Apolipoproteínas A/genética , Doenças Cardiovasculares/genética , LDL-Colesterol/genética , Colesterol/genética , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína A-V , Brasil , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Alzheimer's Disease (AD) is the most common cause of dementia in elderly people. The presynaptic terminal is an important site of pathological changes in AD, leading to synaptic loss in specific brain regions, such as in the cortex and hippocampus. In this study, we investigated synaptosomal-associated protein, 25-kDa (SNAP25) mRNA levels and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood leukocytes of young, healthy elderly and AD patients. mRNA quantification was performed by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) using the ΔΔC(T) method and promoter DNA methylation was quantified by mass spectrometry using the Sequenom EpiTYPER platform. We observed a significant decrease in SNAP25 expression in AD across all the three brain regions in relation to the healthy elderly subjects, suggesting impairment in synaptic function. The changes in the auditory cortex reflected those observed in the hippocampus and entorhinal cortex, the primary areas affected in AD. However, no AD-associated differences in SNAP25 promoter DNA methylation were observed suggesting that other mechanisms may be involved in mediating the observed gene expression changes.
Assuntos
Doença de Alzheimer/genética , Encéfalo/metabolismo , Metilação de DNA/genética , Regiões Promotoras Genéticas/genética , Proteína 25 Associada a Sinaptossoma/genética , Idoso , Doença de Alzheimer/metabolismo , Feminino , Humanos , Masculino , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Proteína 25 Associada a Sinaptossoma/biossíntese , Sinaptossomos/metabolismo , TranscriptomaRESUMO
Lipoprotein lipase is essential for triglyceride hydrolysis. The polymorphisms S447X in exon 9 and HindIII in intron 8 have been associated with lower triglyceride levels and lower cardiovascular risk in adult men. We examined the association of these lipoprotein lipase polymorphisms with high-density lipoprotein (HDL) and triglyceride levels in elderly men. Blood samples were obtained from 87 elderly men, 48 of whom had cardiovascular disease and 39 (controls) had no history of cardiovascular events. The lipoprotein lipase polymorphisms were analyzed by PCR-RFLP. Allele frequencies were H- = 27.9% and X = 21.5%. There were no significant differences in allele frequencies or blood lipid levels between cardiovascular disease and control groups. However, the X allele was associated with a lower triglyceride/HDL ratio, 2.30 vs 3.02 for X allele absent (P = 0.03); the H-X haplotype was associated with lower triglyceride levels compared to the H+S haplotype (1.22 vs 1.58 mM, respectively) and a lower triglyceride/HDL ratio (2.29 vs 3.26, respectively). The X allele and H-X haplotype were associated with lower triglyceride/HDL ratios in these elderly men, independent of the history of cardiovascular events.
RESUMO
Lipoprotein lipase is essential for triglyceride hydrolysis. The polymorphisms S447X in exon 9 and HindIII in intron 8 have been associated with lower triglyceride levels and lower cardiovascular risk in adult men. We examined the association of these lipoprotein lipase polymorphisms with high-density lipoprotein (HDL) and triglyceride levels in elderly men. Blood samples were obtained from 87 elderly men, 48 of whom had cardiovascular disease and 39 (controls) had no history of cardiovascular events. The lipoprotein lipase polymorphisms were analyzed by PCR-RFLP. Allele frequencies were H- = 27.9% and X = 21.5%. There were no significant differences in allele frequencies or blood lipid levels between cardiovascular disease and control groups. However, the X allele was associated with a lower triglyceride/HDL ratio, 2.30 vs 3.02 for X allele absent (P = 0.03); the H-X haplotype was associated with lower triglyceride levels compared to the H+S haplotype (1.22 vs 1.58 mM, respectively) and a lower triglyceride/HDL ratio (2.29 vs 3.26, respectively). The X allele and H-X haplotype were associated with lower triglyceride/HDL ratios in these elderly men, independent of the history of cardiovascular events.
Assuntos
Lipase Lipoproteica/genética , Lipoproteínas HDL/sangue , Triglicerídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Brasil , Desoxirribonuclease HindIII/química , Éxons , Frequência do Gene , Genes Ligados ao Cromossomo X , Haplótipos , Humanos , Íntrons , Masculino , Polimorfismo GenéticoRESUMO
TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72) polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia), and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg) = 0.69 and P (Pro) = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Doenças Cardiovasculares/genética , Códon/genética , /genética , Polimorfismo Genético/genética , Brasil , Doenças Cardiovasculares/sangue , Métodos Epidemiológicos , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Reação em Cadeia da PolimeraseRESUMO
TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72) polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia), and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg) = 0.69 and P (Pro) = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.