Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid levels in an older adult/elderly cohort
ABSTRACT Background and Aims: The characterization of candidate gene polymorphisms in elderly populations is an important tool for the identification of risk factors for age-related diseases and conditions. We aimed to genotype the APOE polymorphisms (rs429358 and rs7412), rs61886492 (1561C>T) and rs202720 of GCPII gene and rs3918242 (-1562C>T) of MMP9 gene in an older-adult/elderly cohort from Cuiaba city, Mato Grosso Brazil as well as to characterize risk factors for morbidities and conditions affecting this cohort. Methods: The studied population consisted of 570 subjects from Cuiaba city, Brazil, who were subjected to clinical interviews and blood collection for laboratory examinations and DNA extraction. Restriction fragment length polymorphism Polymerase Chain Reaction (RFLP-PCR), sequence-specific primer PCR (SSP-PCR) and TaqMan® allelic discrimination assay were used for genotyping. Results: The frequencies of APOE ε2 and ε4 were 6.6% and 14.8%, respectively, and the frequencies of GCPII rs61886492 T allele, GCPII rs202720 C allele and MMP9 rs3918242 T allele were, respectively, 3.0%, 26.6% and 10.1%. Significant associations between APOE ε2 allele with lower total cholesterol and LDL-cholesterol were found. In addition, MMP9 rs3918242 T allele was associated with higher LDL-cholesterol levels, suggesting a link between lipid metabolism alteration and cardiovascular disease. Conclusions: The present findings contributed to characterize risk factors specific for the studied population and to better understand the molecular physiopathology of common morbidities and conditions affecting older-adult/elderly people.
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ABSTRACT: Treatment of hypertension reduces vascular dementia (VaD) risk but not all anti-hypertensive drugs (AHDs) are equally effective, suggesting drug-gene interactions. To understand this relationship, publicly accessible databases were searched for genes deregulated in VaD and their interactions with AHDs. Genes that were downregulated in association with VaD were MTHFR, SYK, AGT, and RPGRIP1L. Genes that were upregulated in VaD were MMP9 and VEGFA. TNFSF14, AR, and PHLDB2 were also associated with VaD, however, transcription or protein level changes could not be ascertained. Analysis of gene expression data suggests that AHDs differentially regulate VaD-associated genes. Information about AHD up- or downregulation of VaD-associated genes could be used as an empirical basis for the optimal selection of AHDs in clinical trials and, ultimately, for VaD prevention and treatment.Journal of Alzheimer's disease: JAD 07/2014; 42. DOI:10.3233/JAD-140003 · 3.61 Impact Factor
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ABSTRACT: Inflammatory periodontal diseases may be associated with common systemic conditions and, as recently described, alterations in lipid levels in the blood. The aim of this study was to determine the possible effects of apolipoprotein E (ApoE) genotypes on the lipid levels in healthy people and patients with chronic periodontitis (CP) in relation to periodontopathic bacteria. This case-control study comprised 469 unrelated subjects. The genomic DNA of 294 patients with CP and 175 healthy/non-periodontitis controls were genotyped, using the real-time polymerase chain reaction (RT-PCR) method, for ApoE (rs429358 and rs7412) gene polymorphisms. Subgingival bacterial colonization was investigated by the DNA microarray using a periodontal pathogen detection kit and lipid levels were measured in a subgroup of subjects (N=275). There was no evidence for a significant association between ApoE gene polymorphisms and CP (P>0.05). Patients with CP had increased levels of total cholesterol and low-density lipoprotein (LDL) compared to controls (P<0.05); however, no significant difference was found for triglyceride and high-density lipoprotein (HDL) levels. ApoE gene variability influenced LDL levels marginally (P=0.08) but it did not modify total cholesterol, triglyceride, and HDL levels or the occurrence of periodontal pathogens in subgingival pockets.(23) CONCLUSIONS: In the Czech population studied, ApoE genetic variations were not associated with susceptibility to CP or the presence of periodontopathic bacteria. Copyright © 2014 Elsevier Ltd. All rights reserved.Archives of Oral Biology 10/2014; 60(3):456-462. DOI:10.1016/j.archoralbio.2014.10.003 · 1.88 Impact Factor
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ABSTRACT: Genetic susceptibility to obstructive sleep apnea (OSA) has been a research focus in the scientific community in the past few years. In this study, we recruited 375 subjects to investigate whether functional polymorphisms in the promoter region of matrix metalloproteinase (MMP)-2 (-1306C/T) and MMP-9 (-1562C/T) increased susceptibility to OSA. Our study showed no significant association between MMP-2 -1306C/T polymorphism and risk of OSA (T vs. C: OR = 1.01, 95% CI = 0.67-1.52; P = 0.97). Compared with the MMP-9 -1562C allele, the -1562T allele was associated with increased risk of OSA (T vs. C: OR = 1.56, 95% CI = 1.02-2.39; P = 0.04). However, neither MMP-2 -1306C/T nor MMP-9 -1562C/T polymorphism was found to be associated with severity of the disease. Our study suggested that the MMP-2 -1306C/T polymorphism was not associated with OSA susceptibility, whereas the MMP-9 -1562T allele was associated with increased risk of OSA.Scientific Reports 03/2015; 5:8966. DOI:10.1038/srep08966 · 5.58 Impact Factor