29
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Meta-Analysis of miR-146a Polymorphisms Association with Coronary Artery Diseases and Ischemic Stroke

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Coronary artery disease (CAD) and ischemic stroke (IS) are manifestations of atherosclerosis, with a high death rate. miR-146a is a microRNA that participates in the progress of CAD and IS. A single nucleotide polymorphism (SNP) in the precursor of miR-146a, rs2910164, was found to be associated with the risks of CAD and IS. However, the results were inconsistent and inconclusive. A meta-analysis was performed to assess the relationship of rs2910164 and CAD as well as IS susceptibility. The database Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM) were searched for related studies. Crude odds ratios with 95% confidence intervals were used to investigate the strength of the association by random- or fixed-effect model. A total of eight studies, with 3138 cases and 3097 controls were identified for the meta-analysis. The results shows that rs2910164 is associated with the risk of CAD significantly in allelic model (OR = 0.86), homozygous model (OR = 0.70), heterozygous model (OR = 0.80) and dominant model (OR = 0.76). The subjects carrying the GG genotype, GG + GC genotype or G allele are at lower risks of CAD. For the susceptibility of IS, there are no significant associations between rs2910164 and total studies. However, in subgroup analysis by sample size and ethnicity, the GG, GG + GC and G allele of rs2910164 are found to be associated with higher risks of IS in large sample size group and in Koreans, under homozygous and dominant models. In conclusion, the current meta-analysis suggests lower risks of CAD for GG, GG + GC genotype and G allele of rs2910164, while rs2910164 is not associated with the risk of IS. Thus rs2910164 might be recommended as a predictor for susceptibility of CAD, but not IS.

          Related collections

          Most cited references17

          • Record: found
          • Abstract: found
          • Article: not found

          Stroke and stroke care in China: huge burden, significant workload, and a national priority.

          At the same time as the world recognizes the rapid economic development in China, Chinese healthcare system has also had significant improvement. However, this nation of 1.4 billion faces tough challenges in treating stroke, the leading cause of death in China. The recently completed Chinese National Stroke Registry has provided new information on the status of stroke epidemiology, diagnosis, management, and prevention strategies in China. In this article, we summarized these new findings, described the effort of providing and improving stroke care, and illustrated the challenges in risk factor modification and secondary stroke prevention. Well-designed epidemiological surveys and clinical trials for stroke prevention and management are still urgently needed in China.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            MicroRNA-146a regulates both transcription silencing and translation disruption of TNF-α during TLR4-induced gene reprogramming.

            Following the TLR-dependent initiation phase of acute systemic proinflammatory responses such as sepsis, an adaptive phase represses or activates a specific pattern of gene expression until the inflammation resolves. Here, we used the THP-1 sepsis cell model of bacterial LPS/endotoxin tolerance to show that TLR4-induced miR-146a supports the feed-forward adaptive processes that silence transcription and disrupt translation of acute proinflammatory genes. First, we found that miR-146a regulates a pathway that promotes the binding of transcription repressor RelB to the TNF-α promoter, a step known to precede histone and DNA modifications, which generate facultative heterochromatin to silence acute proinflammatory genes. However, once RelB binding occurred, miR-146a inhibition could not reverse compacted chromatin, and endotoxin tolerance persisted. Second, we observed that miR-146a regulates a pathway that supports assembly of the translation repressor complex of TNF-α by preventing the interaction of the RNA-binding protein effector Ago2 and RBM4. We also determined that once endotoxin tolerance is established, and specific genes have been reprogrammed, transcription and translation disruption can be reversed only by simultaneously depleting RelB and inhibiting miR-146a. Thus, miR-146a induction supports the TLR4-dependent shift from initiation to gene-specific repression at two levels. Our results also imply that therapies designed to reverse endotoxin tolerance as potential therapies for sepsis should be directed at the transcription and translation pathways of reprogramming.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Association of the miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with ischemic stroke and silent brain infarction risk.

              MicroRNAs play a role in atherosclerosis-related diseases, such as cerebrovascular or cardiovascular disease. However, the effect of miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms on stroke and silent brain infarction (SBI) susceptibility has not been reported. Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 678 patients with ischemic stroke, 373 patients with SBI, and 553 control subjects. The miR-146aC>G polymorphism and miR-146aG/-149T/-196a2C/-499G allele combination was significantly associated with ischemic stroke prevalence. For SBI prevalence, there were no statistically significant genetic markers. However, some allele combinations were associated with increased SBI incidence (C-T-C-G and G-T-T-A of miR-146a/-149/-196a2/-499). In subgroup analyses, miR-146aC>G increased stroke risk in female, normotensive, and nondiabetic groups. There were significant combined effects between microRNA polymorphisms and homocysteine/folate levels on ischemic stroke and SBI prevalence. The miR-146aG allele and miR-146aG/-149T/-196a2C/-499G allele combination were associated with ischemic stroke pathogenesis. The combined effects between microRNA polymorphisms and homocysteine/folate levels may contribute to stroke and SBI prevalence.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                24 June 2015
                July 2015
                : 16
                : 7
                : 14305-14317
                Affiliations
                [1 ]Department of Anatomy, Histology and Embryology, Changsha Medical University, Changsha 410219, China; E-Mails: zhangqingsong@ 123456whut.edu.cn (Q.-S.Z.); luohuaiqing@ 123456163.com (H.-Q.L.); luoji927@ 123456163.com (J.L.); zhaojuannanfang2@ 123456163.com (J.Z.); liguangyi1977@ 123456163.com (G.-Y.L.); zengjie84117@ 123456163.com (J.Z.)
                [2 ]Qingdao Science & Standard Chemicals Analysing and Testing Co., Ltd., Qingdao 266000, China; E-Mail: y_xiao@ 123456sscta.cn
                Author notes
                [* ]Authors to whom correspondence should be addressed; E-Mails: mhbao78@ 123456163.com (M.-H.B.); ljming0901@ 123456sina.com (J.-M.L.); Tel.: +86-731-8488-4488 (M.-H.B.); Fax: +86-731-8849-8866 (M.-H.B.).
                Article
                ijms-16-14305
                10.3390/ijms160714305
                4519843
                26114385
                923d63c7-fcc4-4e3f-8c0d-5f517fd81fa9
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 April 2015
                : 09 June 2015
                Categories
                Article

                Molecular biology
                mir-146a polymorphism,rs2910164,coronary artery disease,ischemic stroke,meta-analysis

                Comments

                Comment on this article