Alzheimer's disease (AD) is a disabling neurodegenerative disorder that leads to long-term functional and cognitive impairment and greatly reduces life expectancy. Early genetic studies focused on tracking variations in genome-wide DNA sequences discovered several polymorphisms and novel susceptibility genes associated with AD. However, despite the numerous risk factors already identified, there is still no fully satisfactory explanation for the mechanisms underlying the onset of the disease. Also, as with other complex human diseases, the causes of low heritability are unclear. Epigenetic mechanisms, in which changes in gene expression do not depend on changes in genotype, have attracted considerable attention in recent years and are key to understanding the processes that influence age-related changes and various neurological diseases. With the recent use of massive sequencing techniques, methods for studying epigenome variations in AD have also evolved tremendously, allowing the discovery of differentially expressed disease traits under different conditions and experimental settings. This is important for understanding disease development and for unlocking new potential AD therapies. In this work, we outline the genomic and epigenomic components involved in the initiation and development of AD and identify potentially effective therapeutic targets for disease control.
- MeSH
- Alzheimerova nemoc genetika patologie MeSH
- epigeneze genetická * MeSH
- genetická predispozice k nemoci * MeSH
- genomika metody MeSH
- lidé MeSH
- metylace DNA * MeSH
- regulace genové exprese * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The frailty syndrome is a common clinical marker of vulnerability in older adults conducive to an overall decline in inflammatory stress responsiveness; yet little is known about the genetic risk factors for frailty in elderly. Our aim was to investigate the association between the rs2476601 polymorphism in PTPN22 gene and susceptibility to frailty in Mexican older adults. Data included 630 subjects 70 and older from The Coyoacán cohort, classified as frail, pre-frail, and non-frail following Fried's criteria. Sociodemographic and clinical characteristics were compared between groups at baseline and after a multivariate analysis. The rs2476601 polymorphism was genotyped by TaqMan genotyping assay using real-time PCR and genotype frequencies were determined for each frailty phenotype in all participants and subsets by age range. Genetic association was examined using stratified and interaction analyses adjusting for age, sex and variables selected in the multivariate analysis. Disability for day-life activities, depression and cognitive impairment were associated with the risk of pre-frailty and frailty at baseline and after adjustment. Carrying the T allele increased significantly the risk of frailty in patients 76 and older (OR 5.64, 95% CI 4.112-7.165) and decreased the risk of pre-frailty under no clinical signs of depression (OR 0.53; 95% CI 0.17-1.71). The PTPN22 polymorphism, rs2476601, could be a genetic risk factor for frailty as subject to quality of life. This is the first study analyzing such relationship in Mexican older adults. Confirming these findings requires additional association studies on wider age ranges in populations of older adults with frailty syndrome.
- MeSH
- alely MeSH
- fenotyp MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie * MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus genetika MeSH
- kohortové studie MeSH
- křehkost genetika patofyziologie MeSH
- křehký senior MeSH
- kvalita života MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tyrosinfosfatasa nereceptorového typu 22 genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Mexiko MeSH