An A/G polymorphism rs3746444 in miR-499 is associated with increased cancer risk: a meta-analysis

Abstract

ABSTRACT. An A/G polymorphism (rs3746444) has been identified in the miR-499 gene that can change the conformation of the secondary gene structure and thereby directly affect binding to target mRNAs and the microRNA (miRNA) maturation process, thus altering protein expression and potentially contributing to cancer susceptibility. Numerous studies investigating the association between the rs3746444 polymorphism and cancers have been published; however, results are inconsistent and inconclusive. To clarify the relationship between the miR-499 rs3746444 polymorphism and cancer, we conducted a comprehensive meta-analysis on 14 case-control studies comprising 7189 cases and 8577 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by using dominant, recessive, and co-dominant genetic models. A publication bias test and subgroup analysis were also performed. Results showed that the G allele was associated with a significantly increased cancer risk compared to the A allele (OR = 1.09; 95%CI = 1.00-1.18). Similarly, moderately elevated risks were also observed in overall analyses in the dominant model (OR = 1.13; 95%CI = 1.01-1.26). Moreover, significantly increased risks were observed in Asian populations (G allele vs A allele: OR = 1.18; 95%CI = 1.01-1.37; GG vs AA: OR = 1.36; 95%CI = 1.07-1.73; dominant model: OR = 1.19; 95%CI = 1.00-1.41; recessive model: OR = 1.31; 95%CI = 1.03-1.66), but not in European populations. These findings indicate that the miR-499 rs3746444 polymorphism is associated with an increased cancer risk.

Let-7 related genetic variation and risk of metabolic syndrome in a Chinese population

“…of human genome [10]. Recently, various studies focused on the pre-miRNA polymorphisms located on the stem-loop, such as pre-mir-196a2 rs11614913 [20], pre-mir-146a rs2910164 [21], pre-mir-499 rs3746444 [22,23]. In the present study, the G allele of pre-let7d rs10993081 was found to contribute an independent increased risk for MetS and this association may be partially due to its effect on glucose metabolism.…”

A New Polymorphism Biomarker rs629367 Associated with Increased Risk and Poor Survival of Gastric Cancer in Chinese by Up-Regulated miRNA-let-7a Expression

“…Thus, pri- and pre-miRNA polymorphisms may be used as genetic markers for predicting cancer risk[32], [34], which have more advantage and strengths than coding gene polymorphisms at the predicting potential because miRNAs frequently located in cancer-associated genomic regions [35] and could regulate almost all the encoding genes [36]. Recently, various studies focused on the pre-miRNA polymorphisms located on the stem-loop, such as pre-mir-196a2 rs11614913 [37], pre-mir-146a rs2910164 [38], pre-mir-499 rs3746444 [39], [40], pre-mir-149 rs2292832 [41], pre-mir-27a rs895819 [42]. Because of the complexity of RNA space structure, increasing attention had been paid to SNP on pri-miRNA.…”

Two SNAP-25 genetic variants in the binding site of multiple microRNAs and susceptibility of ADHD: A meta-analysis

“…The statistical power of an individual study can be limited for efficient assessment of the polymorphism, and therefore, integration of these data sets are needed to provide improved statistical power to detect significant effects (Wang et al, 2013). Meta-analysis is a method of increasing the effective sample size through the pooling of data from individual studies in order to increase the power to estimate, in this case, the genetic effect.…”