MiR-196a2 rs11614913 polymorphism could not influence coronary artery disease risk in Asians
- *Corresponding Author:
- Zhi-Ling He
Department of Caridiovascular
The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, PR China
Accepted date: May 05, 2017
Although some studies have investigated the association between miR-196a2 rs11614913 polymorphism and coronary artery disease (CAD) risk. The effect of miR-196a2 rs11614913 polymorphism on CAD susceptibility remain unknown. This meta-analysis aimed to determine this association. PubMed and EMBASE were searched to find relevant studies which investigated the association between miR-196a2 rs11614913 polymorphism and CAD risk. Five case-control studies including 3370 CAD patients and 3011 controls were included in this meta-analysis. MiR-196a2 rs11614913 polymorphism was not associated with CAD risk in the allelic model (OR=1.02; 95% CI 0.95-1.09; P=0.67). Additionally, no significant results were found in other genetic models. In conclusion, we found that miR-196a2 rs11614913 polymorphism played no role in CAD risk in Asians.
MicroRNAs, Coronary artery disease, Genetic, Polymorphism.
MicroRNAs are small non-coding RNAs of approximately 22 nucleotides long . They could regulate target mRNA translation through complementary binding in the 3' untranslated region (3' UTR) of mRNAs . MicroRNAs carry pervasive transcriptional and posttranscriptional regulatory actions relevant to human health and disease, including coronary artery disease (CAD). Labbaf et al. suggest that miR-499-rs3746444-GG is associated with CAD susceptibility and development . Faccini et al. demonstrated that the combination of the three circulating miRNA managed to deliver a specific signature for diagnosing CAD . Liu et al. suggested that miR-208b may serve as a sensitive biomarker for the diagnosis and prognosis of acute myocardial infarction patients . Although some studies have investigated the association between miR-196a2 rs11614913 polymorphism and CAD risk [5-9]. The effect of miR-196a2 rs11614913 polymorphism on CAD susceptibility remains unknown. This meta-analysis aimed to determine this association.
Materials and Methods
PubMed and EMBASE were searched to find relevant studies which investigated the association between miR-196a2 rs11614913 polymorphism and CAD risk. The keywords included: “coronary artery disease” or CAD and “miR-196a2”. There was no language and time restriction.
Inclusion and exclusion criteria
Studies were included if they met the following criteria: (1) case–control study; (2) about the association between miR-196a2 rs11614913 polymorphism and CAD risk; and (3) had available genotype frequencies of cases and controls or could be calculated from the paper. Accordingly, the exclusion criteria were (1) duplicate data, (2) abstract, reviews, and animal studies, (3) only included CAD patients.
Two authors extracted the data from included studies independently. The following data were collected from each study: the first author, year, country, ethnicity, sample size, and numbers of genotype.
The strength of association between miR-196a2 rs11614913 polymorphism and CAD risk was estimated by OR with corresponding 95% CI. Q-statistic was applied to investigate heterogeneity among studies. P-value greater than 0.1 for Q test suggested a lack of statistically significant heterogeneity, and the fixed-effect model (Mantel-Haenszel method) was used to calculate pooled ORs. Otherwise, heterogeneity was present and the random-effect model (DerSimonian-Laird method) was more appropriate. Potential publication bias was estimated by symmetry of funnel plot. All statistical tests in this metaanalysis were two-tailed and P-value<0.05 was considered statistically significant unless otherwise noted. Data analysis was performed using Revman 5.1.
Characteristics of the studies
Characteristics the included studies are listed in Table 1. Five case-control studies including 3370 CAD patients and 3011 controls were included in this meta-analysis. All these studies were conducted in Asians.
Table 1: Characteristics of studies.
The results of the association between miR-196a2 rs11614913 polymorphism and CAD risk are summarized in Table 2. As shown in Figure 1, miR-196a2 rs11614913 polymorphism was not associated with CAD risk in the allelic model (OR=1.02; 95% CI 0.95-1.09; P=0.67). Additionally, no significant results were found in other genetic models (Table 2). Funnel plot was performed to assess the publication bias of literatures. The shape of the funnel plot did not reveal any evidence of obvious asymmetry (Figure 2).
|P heterogeneity||Model||OR (95% CI)||P value|
|C vs. T||0.57||F||1.02 (0.95-1.09)||0.67|
|CC vs. TT||0.53||F||1.14 (1.00-1.29)||0.05|
|CC vs. CT||0.56||F||0.98 (0.87-1.11)||0.74|
|CC vs. TT+CT||0.90||F||0.99 (0.87-1.11)||0.81|
|CC+CT vs. TT||0.11||F||0.98 (0.92-1.05)||0.55|
Table 2: Meta-analysis results.
The current study used a comprehensive meta-analysis to reveal an miR-196a2 rs11614913 polymorphism and CAD risk. We found that individuals with miR-196a2 rs11614913 polymorphism did not show significant results in the Asians population. However, this association should be confirmed in Caucasians, since no study using Caucasians was included. The role of miR-196a2 rs11614913 polymorphism in diseases has been studied extensively. Yu et al. suggested that the C allele of the rs11614913 (T>C) SNP of miR-196a2 are associated with a significantly reduced risk of ASD . Hussein et al. found that microRNA-196a2 rs11614913 polymorphism might be associated with asthma severity in our sample of the Egyptian population . Chen et al. suggested that MIR196A2 rs11614913 polymorphism may contribute to an increased risk of hepatopulmonary syndrome in liver cirrhosis patients .
Some limitations in this meta-analysis should be addressed. First, only published studies were included; it was possible that some relevant published or unpublished studies may have been missed. Second, lacking of the original data of the eligible studies limited the evaluation of the subgroup analyses by gender, age, and other factors. Finally, all the studies were conducted in Asians, no study from other races was included.
In conclusion, we found that miR-196a2 rs11614913 polymorphism played no role in CAD risk in Asians.
This work supported by Science and Technology Research Program of Traditional Chinese Medicine of Guangdong Province Hospital of Traditional Chinese Medicine (No. YN2014LN06).
- Bartel DP. MicroRNAs: target recognition and regulatory functions. Nat Rev Cancer 2015; 15: 321-333.
- Labbaf A, Ghaedi H, Alipoor B, Omrani MD, Kazerouni F, Shanaki M, Ghaffarzadeh M, Pashaiefar H, Rahimipour A. The pre-mir-499 Variant rs3746444 May Contribute to Coronary Artery Disease Susceptibility: a Case-Control and Meta-Analysis Study. Clin Lab 2017; 63: 587-595.
- Faccini J, Ruidavets JB, Cordelier P, Martins F, Maoret JJ, Bongard V, Ferrires J, Roncalli J, Elbaz M, Vindis C. Circulating miR-155, miR-145 and let-7c as diagnostic biomarkers of the coronary artery disease. Sci Rep 2017; 7: 42916.
- Liu X, Yuan L, Chen F, Zhang L, Chen X, Yang C, Han Z. Circulating miR-208b: A Potentially Sensitive and Reliable Biomarker for the Diagnosis and Prognosis of Acute Myocardial Infarction. Clin Lab 2017; 63: 101-109.
- Zhi H, Wang L, Ma G, Ye X, Yu X, Zhu Y, Zhang Y, Zhang J, Wang B. Polymorphisms of miRNAs genes are associated with the risk and prognosis of coronary artery disease. Clin Res Cardiol 2012; 101: 289-296.
- Chen C, Hong H, Chen L, Shi X, Chen Y, Weng Q. Association of microRNA polymorphisms with the risk of myocardial infarction in a Chinese population. Tohoku J Exp Med 2014; 233: 89-94.
- Huang S, Lv Z, Deng Q, Li L, Yang B, Feng J, Wu T, Zhang X, Cheng J. A Genetic Variant in Pre-miR-146a (rs2910164 C>G) Is Associated with the Decreased Risk of Acute Coronary Syndrome in a Chinese Population. Tohoku J Exp Med 2015; 237: 227-233.
- Xiong XD, Cho M, Cai XP, Cheng J, Jing X, Cen JM, Liu X, Yang XL, Suh Y. A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression. Mutat Res 2014; 761: 15-20.
- Sung JH, Kim SH, Yang WI, Kim WJ, Moon JY, Kim IJ, Cha DH, Cho SY, Kim JO, Kim KA, Kim OJ, Lim SW, Kim NK. miRNA polymorphisms (miR‑146a, miR‑149, miR‑196a2 and miR‑499) are associated with the risk of coronary artery disease. Mol Med Rep 2016; 14: 2328-2342.
- Yu K, Ji Y, Wang H, Xuan QK, Li BB, Xiao JJ, Sun W, Kong XQ. Association of miR-196a2, miR-27a, and miR-499 polymorphisms with isolated congenital heart disease in a Chinese population. Genet Mol Res 2016; 15.
- Hussein MH, Toraih EA, Aly NM, Riad E, Fawzy MS. A passenger strand variant in miR-196a2 contributes to asthma severity in children and adolescents: A preliminary study. Biochem Cell Biol 2016; 94: 347-357.
- Chen HY, Chen YM, Wu J, Yang FC, Lv Z, Xu XF, Zheng SS, Liao SS, Luo YH. MIR196A2 rs11614913 C>T polymorphism correlates with an increased risk of hepatopulmonary syndrome in liver cirrhosis: a case-control study in China. Hepatol Res 2016.