Search

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. However, biomarkers that require testing in the brain tissue pose a formidable practical barrier to AD diagnostic innovation. MicroRNAs (miRNAs) are responsible for control of gene expression at the posttranscriptional level and are essential for the function of neuronal networks and neuronal survival. miRNA expression can impact the regulation of APP (amyloid beta A4 precursor protein), PSEN1 (presenilin 1), PSEN2 (presenilin 2), and BACE1 (beta-secretase 1) genes in the brain that were previously implicated in AD pathophysiology. Little is known, however, on the extent to which peripheral tissue (e.g., whole blood) miRNA variation might offer clinical predictive value for AD. Moreover, few studies have examined multiple peripheral miRNA expression data at the same time. We report here, to the best of our knowledge, the first whole-blood-based and parallel study of seven miRNAs ( hsa-miR-9-5p, hsa-miR-29a-3p, hsa-miR-106a-5p, hsa-miR-106b-5p, hsa-miR-107, hsa-miR-125a-3p, and hsa-miR-125b-5p) in relation to AD susceptibility. Notably, these miRNAs are situated 'upstream' to the genes implicated in AD. We measured the whole-blood miRNA expression by a real-time polymerase chain reaction in a large study sample ( n = 281), comprising patients with AD ( n = 172) and healthy controls ( n = 109). A reduction in whole-blood expression of hsa-miR-9-5p, hsa-miR-106a-5p, hsa-miR-106b-5p, and hsa-miR-107 was significantly associated with an increased risk of AD ( p < 0.05). Notably, after receiver operating characteristics curve analyses, hsa-miR-106a-5p displayed, as a predictor variable, 93% specificity and 68% sensitivity. On the other hand, the expression of hsa-miR-29a-3p, hsa-miR-125a-3p, and hsa-miR-125b-5p was not significantly different between patients and controls ( p > 0.05). In conclusion, these observations warrant replication in larger samples while making a contribution to translational research, precision medicine, and biomarker literatures, by expanding the current efforts for AD diagnostic innovation to the realm of epigenomic pathways such as miRNA expression variation among patients. [ABSTRACT FROM AUTHOR]

Alcohol dependence (AD) is a neuropsychiatric disorder to which both genetic and environmental factors contribute. Especially, multiple genetic factors are promising to explain the etiology of AD. microRNAs (miRNAs) are members of a family of noncoding small RNAs, which are thought to be responsible for the altered gene expression in neuropsychiatric disorders. We hypothesized that single nucleotide polymorphisms (SNPs) in the miRNA biogenesis pathway may result in dysregulation of miRNA levels inside the cell. The aim of this study was to test an association between miRNA biogenesis gene variants and AD risk. Real-time polymerase chain reaction genotyping experiment was conducted on DNA samples from 123 alcohol-dependent patients and 135 healthy controls. We found that AGO1 rs595961 ( χ2=9.066, p=0.003; odds ratio [OR]=0.459, 95% confidence interval [CI]: 0.275-0.768) and AGO2 rs4961280 ( χ2=4.111, p=0.043; OR=0.590, 95% CI: 0.353-0.986) G alleles have significantly altered the risk for AD, and also there is a significant association of GEMIN4 rs910924 ( χ2=5.291, p=0.021; OR=1.913, 95% CI: 1.094-3.344) T allele with the risk for AD. We also found statistically significant difference in AGO1 rs595961 ( χ2=11.139, p=0.001) and DGCR8 rs1640299 ( χ2=13.001, p=0.002) genotype frequencies between case-control groups. This is the first study to investigate the effects of SNPs in the miRNA biogenesis pathway on AD risk. In conclusion, we identified a significant association of miRNA biogenesis genes with altered AD risk, and these results could be a guide to research on the role of miRNAs in AD in the future. [ABSTRACT FROM AUTHOR]

It was aimed to investigate the association of the synapsin III gene −196 G> A and −631 C>G polymorphisms that takes place in an encoding presynaptic protein, with adult attention deficit hyperactivity disorder (ADHD). One hundred thirty-nine patients having adult ADHD and 106 controls were included in the study. DNA samples were extracted from whole blood and genetic analyses were performed. A significant difference was determined between ADHD and synapsin III gene −631 C>G polymorphism compared to the control group. No significant difference was determined between ADHD and synapsin III gene −196 G>A polymorphism. These polymorphisms were found not to be associated with subtypes of ADHD. It is supposed that synaptic protein genes together with dopaminergic genes might have roles in the etiology of ADHD. Association of synapsin III gene with adult attention deficit hyperactivity disorder. One of two polymorphisms in synapsin III studied was found to be associated with ADHD. [ABSTRACT FROM AUTHOR]