APRISMA-compliant systematic review and meta-analysis determining the association of miRNA polymorphisms and risk of congenital heart disease

PURPOSE: Recent genetic association studies showed conflicting results on the relationship of miRNA single-nucleotide polymorphisms (SNPs) and congenital heart disease (CHD) risk. The purpose of the present systematic review was to collect the current available evidences to evaluate the association between miRNA polymorphisms and CHD risk. METHODS: Four electronic databases including PubMed, EMBASE, ISI Web of Science, and CENTRAL were extensively searched for relevant studies published before February, 2019. Observational studies determining the association between miRNA polymorphisms and risk of CHD were included. Risk of bias was evaluated using the Newcastle-Ottawa Scale by 2 independent researchers. Major characteristics of each study and estimation of effect size of individual locus polymorphism were summarized. In addition, meta-analysis was performed to quantify the associations between miRNA polymorphisms and CHD risk. RESULTS: Nine studies containing 6502 CHD patients and 6969 healthy controls were included in this systematic review. Ten loci in 9 miRNAs were reported. Only rs11614913 in miR-196a2 was determined to have significant associations with CHD susceptibility, which was supported by meta-analysis (CC vs CT+TT: odds ratio 1.54, 95% confidence interval 1.30, 1.82; P < .00001). A strong evidence indicated lack of association between rs2910164 in miR-146a and CHD. Limited or conflicting evidences were found for the associations of the other variants (rs11134527, rs139365823, rs76987351, rs3746444, rs4938723, rs2292832, rs41291957, rs895819) and risk of CHD. CONCLUSIONS: Locus polymorphisms in miRNAs are not generally associated with CHD. Only rs11614913 was found to have significant associations with CHD. Further studies will be needed, using larger populations of different ethnicities, to obtain a better understanding of these associations.