Rs3746444 Single-nucleotide Polymorphisms Research Articles

MiR-499a rs3746444 A>G Polymorphism Is Correlated with Type 2 Diabetes Mellitus and Diabetic Polyneuropathy in a Romanian Cohort: A Preliminary Study.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, with little evidence available regarding Caucasians. The aim of the present study was to establish whether four miRNA SNPs (miR-27a rs895819 T>C, miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, and miR-499a rs3746444 A>G) are correlated with susceptibility to T2DM and/or diabetic polyneuropathy (DPN) in a Romanian population. A total of 167 adult T2DM patients and 324 age- and sex-matched healthy controls were included in our study. miRNA SNPs were detected by real-time PCR using a TaqMan genotyping assay. A significant association with T2DM was observed only for the miR-499a rs3746444 A>G SNP in all the tested models, and the frequencies of both the miR-499a rs3746444 AG and the GG genotypes were higher in the T2DM patients compared to the controls. No correlation was observed for the miR-27a rs895819 T>C, miR-146a rs2910164 G>C, or miR-196a2 rs11614913 C>T SNPs in any genetic model. When we assessed the association of these SNPs with DPN separately, we found a positive association for the miR-499a rs3746444 SNP in both codominant and dominant models (OR 6.47, 95% CI: 1.71-24.47; OR 2.30, 95% CI: 1.23-4.29, respectively). In conclusion, this study shows that miR-499a rs3746444 A>G may influence both T2DM and DPN susceptibility, with carriers of the GG genotype and the G allele being at an increased risk in the Romanian population.

The correlation of microRNA-499 rs3746444 T>C locus with the susceptibility of gastric cancer: from a case-control study to a meta-analysis.

The relationship between rs3746444 T>C single-nucleotide polymorphism (SNP) in microRNA (mir)-499 and risk of gastric cancer (GC) has been widely investigated. However, the association was still unconfirmed. Here, we first recruited 490 GC patients and 1476 controls, and conducted a case-control study. And we did not find any association between rs3746444 T>C SNP polymorphism and risk of GC. Subsequently, we conducted a meta-analysis to explore the association of mir-499 rs3746444 polymorphism with GC development. Two authors searched the PubMed and EMBASE databases up to October 15, 2019 independently. Finally, nine literatures involving 12 independent studies were included. In total, 3954 GC cases and 9745 controls were recruited for meta-analysis. The results suggested that allele model, homozygote model and recessive model could increase the risk of overall GC (P = 0.002, 0.009 and 0.013, respectively). When we excluded the studies violated HWE, this association was also found in allele model (P = 0.020) and dominant model (P= 0.044). In subgroup analyses, we identified that rs3746444 SNP in mir-499 increased the risk of GC in Asians and gastric cardiac adenocarcinoma (GCA) subgroups. No significant bias of selection was found (all P>0.1). Test of sensitivity analysis indicated that our findings were stable. Additionally, we found that the power value was 0.891 in the allele model, suggesting the reliability of our findings. In summary, our analysis confirmed the association between rs3746444 and the risk of GC, especially in Asians and in patients with GCA.

Associations of Common Single Nucleotide Polymorphisms in miR-34b/c and miR-499 with Male Infertility Caused by Oligospermia or Azoospermia in the Chinese Population.

Aims: The present study was designed to survey the associations between polymorphisms of the common single nucleotide polymorphism (SNP) rs4938723 in the miR-34b/c gene, as well as the rs3746444 SNP in the miR-499 gene, and impairment of spermatogenesis leading to oligospermia and azoospermia in the Chinese population. Subjects and Methods: Specimens were collected from four hundred seventeen infertile men with oligospermia or azoospermia and 234 controls for this investigation. Polymerase chain reaction and restriction fragment length polymorphism analyses was used for genotyping the rs4938723 and rs3746444 SNPs. A chi-square analysis was used to compare the differences in allelic and genotypic frequencies between patients and controls. Results: The distribution of alleles at the rs3746444 locus of the miR-499 gene in patients was not significantly different from controls. There were, however, significant differences in the genotypic (p = 0.040) and allelic (p = 0.021) distributions of the rs4938723 SNPs between patients with oligospermia and controls. The CC genotype at the rs4938723 locus was significantly higher in in patients with oligospermia than controls (13.9% vs. 7.3%, p = 0.016, odds ratio = 2.064, 95% confidence interval 1.132-3.764). Conclusion: The CC genotype of the rs4938723 locus in the miR-34b/c gene may enhance susceptibility to oligospermia.

Genetic variants of MicroRNA-related genes in susceptibility and prognosis of end-stage renal disease and renal allograft outcome among north Indians

MicroRNAs are important molecules of the innate and adaptive immune system, which may play an important role in maintaining normal immune homeostasis. The aim of this study was to investigate the impact of MIR146A C>G (rs2910164), MIR149 T>C (rs2292832), MIR196A2 T>C (rs11614913), and MIR499A A>G (rs3746444) single nucleotide polymorphisms (SNPs) among end-stage renal disease (ESRD) and acute allograft rejection (AR) cases. Genotyping of MicroRNA SNPs was performed using a PCR, followed by restriction fragment length polymorphism in 350 ESRD patients and 350 age-matched, sex-matched, and ethnically matched controls. We observed an increased risk of almost two-fold for ESRD and three-fold for AR cases under univariate and multivariate models for mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs. Subsequently, no susceptible/protective effect was observed for rs2292832 SNP with ESRD and AR cases. Interestingly, all the SNPs that were significant after multiple comparisons in ESRD and AR cases remained significant in the bootstrap analysis, providing internal validation to our initial observations. Survival analysis showed that the mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs were associated with the lowest overall survival compared with heterozygous and wild genotypes among renal allograft recipients. The crude and adjusted hazard ratios in univariate and multivariate Cox regression models showed an almost two-fold increased risk for overall survival against mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs in renal allograft recipients. These results suggest that the variants of MicroRNA SNPs, namely, rs2910164, rs11614913, and rs3746444, might be involved in susceptibility to ESRD and AR.