Abstract
Background
Mild cognitive impairment is now widely recognized to be a transitional phase between healthy cognitive aging and dementia. Individuals with isolated memory loss termed amnestic mild cognitive impairment (aMCI), which is assumed to be a prodromal stage for Alzheimer’s disease and has a conversion rate at 10-15% per year. MicroRNAs, a number of small non-protein coding RNAs, are involved in protein post-transcriptional expression through binding to messenger RNA. In vitro, microRNA has been shown to be essential in neuronal differentiation and brain morphogenesis. In vivo, altered microRNA expression levels have been detected in cerebrospinal fluid and hippocampus of Alzheimer’s disease patients. Although evidence indicates genetic variations in microRNA should be functional and involved in human disease, their roles in the pathogenesis of dementia is poorly understood. To better understand this, four polymorphisms selected from pre-miRNAs were investigated in Chinese aMCI patients.
Methods
In this pilot study, 78 aMCI patients and 289 normal controls were recruited from the Memory Clinic of Queen Mary Hospital and community elderly social centers in Hong Kong, separately. Four previously published SNPs, including rs2910164, rs11614913, rs3746444, rs2292832, were selected for genotyping. As rs3746444 was failed for Hardy-Weinberg equilibrium test and rs2292832 was failed for primers’ design, only two SNPs were included for further data analysis.
Results
After adjustment for age, sex and APOEε4 status by multivariate logistic analysis, the C allele of rs11614913 in hsa-mir-196a-2 were found to associate with increased aMCI risk (p=0.01, OR=1.62) compared to T allele. Genotypic analysis showed that in recessive model, (CC) genotype of rs11614913 were associated with 2-fold increased disease risk compared to (CT+TT) genotype (p=0.02, OR=1.98). Furthermore, we found that C allele of the polymorphism were negatively correlated with Mini–Mental State Examination score (p=0.0001) and Delayed Word Recall Test score (p=0.002), but positively correlated with Alzheimer's Disease Assessment Scale-Cognitive Subscale score (p=0.003) in our Chinese population. Unfortunately, no significant finding was detected for rs2910164.
Conclusions
Results from our pilot study suggest the involvement of hsa-mir-196a-2 rs11614913 in the pathogenesis of Chinese aMCI patients. Further studies based on larger size should be conducted to validate the potential effect in an independent population.
Mild cognitive impairment is now widely recognized to be a transitional phase between healthy cognitive aging and dementia. Individuals with isolated memory loss termed amnestic mild cognitive impairment (aMCI), which is assumed to be a prodromal stage for Alzheimer’s disease and has a conversion rate at 10-15% per year. MicroRNAs, a number of small non-protein coding RNAs, are involved in protein post-transcriptional expression through binding to messenger RNA. In vitro, microRNA has been shown to be essential in neuronal differentiation and brain morphogenesis. In vivo, altered microRNA expression levels have been detected in cerebrospinal fluid and hippocampus of Alzheimer’s disease patients. Although evidence indicates genetic variations in microRNA should be functional and involved in human disease, their roles in the pathogenesis of dementia is poorly understood. To better understand this, four polymorphisms selected from pre-miRNAs were investigated in Chinese aMCI patients.
Methods
In this pilot study, 78 aMCI patients and 289 normal controls were recruited from the Memory Clinic of Queen Mary Hospital and community elderly social centers in Hong Kong, separately. Four previously published SNPs, including rs2910164, rs11614913, rs3746444, rs2292832, were selected for genotyping. As rs3746444 was failed for Hardy-Weinberg equilibrium test and rs2292832 was failed for primers’ design, only two SNPs were included for further data analysis.
Results
After adjustment for age, sex and APOEε4 status by multivariate logistic analysis, the C allele of rs11614913 in hsa-mir-196a-2 were found to associate with increased aMCI risk (p=0.01, OR=1.62) compared to T allele. Genotypic analysis showed that in recessive model, (CC) genotype of rs11614913 were associated with 2-fold increased disease risk compared to (CT+TT) genotype (p=0.02, OR=1.98). Furthermore, we found that C allele of the polymorphism were negatively correlated with Mini–Mental State Examination score (p=0.0001) and Delayed Word Recall Test score (p=0.002), but positively correlated with Alzheimer's Disease Assessment Scale-Cognitive Subscale score (p=0.003) in our Chinese population. Unfortunately, no significant finding was detected for rs2910164.
Conclusions
Results from our pilot study suggest the involvement of hsa-mir-196a-2 rs11614913 in the pathogenesis of Chinese aMCI patients. Further studies based on larger size should be conducted to validate the potential effect in an independent population.
| Original language | English |
|---|---|
| Journal | Alzheimer's & dementia : the journal of the Alzheimer's Association |
| Volume | 12 |
| Issue number | 7S_Part_21 |
| DOIs | |
| Publication status | Published - 24 Jul 2016 |
| Externally published | Yes |
