Genetic Association of MiR-146a with Multiple Sclerosis Susceptibility in the Chinese Population

被引:52
作者
Li, You [1 ]
Du, Chen [2 ]
Wang, Wei [3 ]
Ma, Guoda [1 ]
Cui, Lili [1 ]
Zhou, Haihong [4 ]
Tao, Hua [4 ]
Yao, Lifen
Zhao, Bin [1 ,4 ]
Li, Keshen [1 ]
机构
[1] Guangdong Med Coll, Affiliated Hosp, Guangdong Key Lab Age Related Cardiac & Cerebral, Zhanjiang 524001, Peoples R China
[2] Harbin Med Univ Canc Hosp, Harbin, Peoples R China
[3] Harbin Med Univ, Affiliated Hosp 1, Dept Neurol, Harbin, Peoples R China
[4] Guangdong Med Coll, Affiliated Hosp, Dept Neurol, Zhanjiang 524001, Peoples R China
关键词
MiR-146a; Multiple sclerosis; Polymorphism; SYSTEMIC-LUPUS-ERYTHEMATOSUS; FUNCTIONAL POLYMORPHISM; RHEUMATOID-ARTHRITIS; EXPRESSION; RISK; MIRNAS; VARIANT; ASTHMA; GAMMA;
D O I
10.1159/000369695
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: miR-146a polymorphisms have been involved in susceptibility to multiple diseases. The aim of the present study was to analyze the potential association between two functional miR-146a polymorphisms (rs2910164 and rs57095329) and multiple sclerosis (MS) in the Han Chinese population. Methods: A cohort of 525 patients and 568 healthy controls were genotyped to detect the two polymorphisms by SNaPshot. Results: No significant differences were detected in the distribution of the two miR-146a polymorphisms between the patients and controls (P > 0.05). However, stratification by gender showed a statistically significant difference in the frequency of the genotype rs2910164 between MS patients and control females (P=0.009). Further stratification analysis by subgroup revealed that the miR-146a rs2910164 C allele conferred a higher risk of developing relapsing-remitting MS (RRMS) (P=0.018). In addition, the rs2910164 C allele was significantly associated with increased expression of miR-146a in patients with RRMS (P=0.025). Moreover, patients with the rs2910164 C allele released more TNF-alpha and IFN-gamma, but not IL-1 beta, compared with individuals carrying the homozygous GG genotype (P < 0.05). Conclusions: Our results provide evidence that rs2910164 may play a role in MS susceptibility in females. The rs2910164 G>C variation may affect the expression of miR-146a and the release of proinflammatory cytokines. Copyright (C) 2015 S. Karger AG, Basel
引用
收藏
页码:281 / 291
页数:11
相关论文
共 35 条
[1]   RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies (Retracted article. See vol. 17, 2016) [J].
Amedei, Amedeo ;
Prisco, Domenico ;
D'Elios, Mario Milco .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2012, 13 (10) :13438-13460
[2]  
[Anonymous], MEDIATORS INFLAMM
[3]   Association between miR-146a rs2910164 polymorphism and autoimmune diseases susceptibility: A meta-analysis [J].
Chen, Hui Fang ;
Hu, Ting Ting ;
Zheng, Xue Yan ;
Li, Mei Qing ;
Luo, Min Hong ;
Yao, Yue Xian ;
Chen, Qing ;
Yu, Shou Yi .
GENE, 2013, 521 (02) :259-264
[4]   Suppression of LPS-induced Interferon-γ and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation [J].
Dai, Rujuan ;
Phillips, Rebecca A. ;
Zhang, Yan ;
Khan, Deena ;
Crasta, Oswald ;
Ahmed, S. Ansar .
BLOOD, 2008, 112 (12) :4591-4597
[5]   Expression and genetic analysis of miRNAs involved in CD4+cell activation in patients with multiple sclerosis [J].
Fenoglio, Chiara ;
Cantoni, Claudia ;
De Riz, Milena ;
Ridolfi, Elisa ;
Cortini, Francesca ;
Serpente, Maria ;
Villa, Chiara ;
Comi, Cristoforo ;
Monaco, Francesco ;
Mellesi, Luisa ;
Valzelli, Stefano ;
Bresolin, Nereo ;
Galimberti, Daniela ;
Scarpini, Elio .
NEUROSCIENCE LETTERS, 2011, 504 (01) :9-12
[6]   Role of gender in multiple sclerosis: Clinical effects and potential molecular mechanisms [J].
Greer, Judith M. ;
McCombe, Pamela A. .
JOURNAL OF NEUROIMMUNOLOGY, 2011, 234 (1-2) :7-18
[7]   miRNAs in neurodegeneration [J].
Hebert, Sebastien S. ;
De Strooper, Bart .
SCIENCE, 2007, 317 (5842) :1179-1180
[8]   Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma [J].
Jazdzewski, Krystian ;
Murray, Elizabeth L. ;
Franssila, Kaarle ;
Jarzab, Barbara ;
Schoenberg, Daniel R. ;
de la Chapelle, Albert .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (20) :7269-7274
[9]   MiR-146a polymorphism is associated with asthma but not with systemic lupus erythematosus and juvenile rheumatoid arthritis in Mexican patients [J].
Jimenez-Morales, S. ;
Gamboa-Becerra, R. ;
Baca, V. ;
Del Rio-Navarro, B. E. ;
Lopez-Ley, D. Y. ;
Velazquez-Cruz, R. ;
Saldana-Alvarez, Y. ;
Salas-Martinez, G. ;
Orozco, L. .
TISSUE ANTIGENS, 2012, 80 (04) :317-321
[10]   MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47 [J].
Junker, Andreas ;
Krumbholz, Markus ;
Eisele, Sylvia ;
Mohan, Hema ;
Augstein, Florian ;
Bittner, Robert ;
Lassmann, Hans ;
Wekerle, Hartmut ;
Hohlfeld, Reinhard ;
Meinl, Edgar .
BRAIN, 2009, 132 :3342-3352