title: A functional polymorphism in the promoter region of microRNA-146a is associated with the risk of Alzheimer disease and the rate of cognitive decline in patients.
abstract: miR146a is well known for its regulatory role in the immune response and inflammation. Recent studies have demonstrated the links between miR146a and Alzheimer disease (AD) and suggested that miR146a may be involved in neuroinflammation and the metabolism of amyloid-β (Aβ), which are critical events in AD pathology. Although genetic studies have focused on the association between the miR146a gene and susceptibility to several diseases, no association study of miR146a variability with AD has been conducted. In this report, we performed a case-control association study to analyze the genotype and allele distributions of the miR146a, rs2910464 and rs57095329 polymorphisms in a Chinese population consisting of 292 AD cases and 300 healthy controls. We found a significant difference in the genotypes and allele frequencies of rs57095329 between the AD cases and the controls (p = 0.0147 and p = 0.0184, respectively), where the AA genotype of rs57095329 was associated with an increased risk of AD as well the cognitive decline in AD patients. Additionally, the AA genotype of rs57095329 exhibited significantly higher miR146a expression than the GG+GA genotypes of rs2910164 in the peripheral blood cells (PBMCs) of healthy individuals and had a stronger effect on the production of IL-6 and IL-1β when the cells were stimulated with LPS. Our data provide preliminary evidence that the rs57095329 polymorphism in the miR146a promoter is involved in the genetic susceptibility to AD, and this risk AA genotype may increase the expression of miR146a and influence certain proinflammatory cytokines, thus playing a role in the pathogenesis of AD.
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Guoda
authors.initials: G
authors.lastname: Ma
authors.affiliation: Clinical Research Center of Guangdong Medical College, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Chronic Disease, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, PR China.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Intensive Care Unit, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Intensive Care Unit, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Yuliu
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China ; Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Gen
authors.initials: G
authors.lastname: Liu
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China ; Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012306:Risk
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C542542:MIRN146 microRNA, human; D035683:MicroRNAs