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 Cuiabá city, Mato Grosso Brazil as well as to characterize risk factors for morbidities and conditions affecting this cohort.
The studied population consisted of 570 subjects from Cuiabá 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.
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.
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.
"Interestingly, patients with multi-infarct and small vessel VaD had more MMP9 protein in the cerebrospinal fluid (CSF) compared to individuals with Alzheimer's disease or healthy controls . Hypertension-induced atherosclerosis was associated with significantly increased levels of MMP9 mRNA  and T allele at the rs3918242 locus was significantly associated with higher LDL-cholesterol levels in females . It is likely therefore, that overexpression is a plausible mechanism of MMP9 contribution to VaD pathology. "
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.