Aim: The study aims to identify high-impact single nucleotide polymorphisms (SNPs) in miRNA target sites of genes associated with lung cancer. Materials & methods: Lung cancer genes were obtained from Uniprot KB. miRNA target site SNPs were mined from MirSNP, miRdSNP and TargetScan. SNPs were shortlisted based on binding impact, minor allele frequency and conservation. Gene expression was analyzed in genes with high-impact SNPs in healthy versus lung cancer tissue. Additionally, enrichment, pathway and network analyzes were performed. Results: 19 high-impact SNPs were identified in miRNA target sites of lung cancer-associated genes. These SNPs affect miRNA binding and gene expression. The genes are involved in key cancer related pathways. Conclusion: The identified high-impact miRNA target site SNPs and associated genes provide a starting point for case-control studies in lung cancer patients in different populations.
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Dual antiplatelet therapy with aspirin and clopidogrel has reduced ischemic vascular events significantly. Genetic influence, especially those in clopidogrel pharmacokinetic-relevant genes partially accounts for interindividual pharmacodynamic variability of clopidogrel. However, most studies have concentrated on the genetic variations in introns, exons, or promoters of the candidate genes, and the association between genetic variations in 3\'-UTR in clopidogrel pharmacokinetic-relevant genes and clopidogrel response is unknown. In our study, ten different algorithms were applied to pick potential miRNAs targeting the clopidogrel pharmacokinetic-relevant genes. Furthermore, the correlation between miRNA expression profiles and mRNA expression of corresponding clopidogrel pharmacokinetic-relevant genes was analyzed. Through comprehensive analysis, including bioinformatics prediction and correlation analysis of miRNA and mRNA expression profiles, miR-218-5p and miR-506-5p were supposed to regulate the expression of PON1 via binding with its 3\'-UTR. Moreover, PON1 rs854551 and rs854552 were located in miRNA recognizing sequences and may serve as potential miRSNPs possibly affecting PON1 expression. The rs854552 polymorphism was genotyped and platelet reactivity index (PRI) indicative of clopidogrel response was measured in 341 Chinese coronary artery disease (CAD) patients 24 h after administration of 300 mg clopidogrel. Our results showed that PON1 rs854552 had a significant influence on PRI in CAD patients, especially in patients with CYP2C19 extensive metabolic phenotype. In conclusion, PON1 rs854552 polymorphisms may affect clopidogrel response. Bioinformatics prediction followed by functional validation could aid in decoding the contribution of unexplained variations in the 3\'-UTR in drug-metabolizing enzymes on clopidogrel response.

OBJECTIVE: MiRSNPs may interfere with mRNA stability through effects on microRNAs (miRNAs)-mRNA interactions via direct changes in miRNA binding site or effect on the secondary structure of this region and changes in accessibility of this region to miRNAs. Studies have confirmed that an elevated level of interleukin-15 receptor alpha (IL-15RA) has an important role in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, for the first time, we aimed to evaluate the possible correlation between a miRSNP, rs2296135, in IL-15RA gene with the risk of SLE and RA.
METHODS: In this case-control study, 100 SLE patients, 100 RA patients, and 110 healthy participants were enrolled to assess rs2296135 genotypes with real-time PCR high-resolution melting method.
RESULTS: According to our findings, AA genotype and A allele of rs2296135 were considerably associated with enhanced risk of RA (for AA genotype, OR = 2.29; 95% CI [1.06-5.02]; for A allele, OR = 1.65; 95% CI [1.10-2.48]). However, this common variant was not significantly correlated with SLE risk in population under study. Stratification analysis in the RA group verified that patients with the A allele had considerably higher serum concentrations of C-reactive protein (CRP) (P < 0.001). In SLE subjects, the frequency of arthritis (P: 0.021) and renal involvement (P: 0.025) in patients with A allele was significantly higher than in other SLE individuals.
CONCLUSIONS: The current study proposes a substantial association between rs2296135 polymorphism in IL-15RA gene with augmented risk of RA and some clinical characteristics in RA and SLE patients.

Aim: The present study was conducted to decipher the inter-relationship of SNPs and miRNAs involved in pharmacogenomics of clopidogrel on predisposition to cardiovascular diseases (CVDs). Materials & methods: A case-control study was conducted on 410 cases and 386 controls to analyze the association of 13 mirSNPs on CVDs risk. Genotyping was performed by tetra-primer amplification refractory mutation system PCR and validated using Sanger DNA sequencing. miRNA expression analysis was performed using TaqMan assays. A meta-analysis was performed for PON1 rs662 with coronary artery disease. Results & conclusion: PON1 rs662, PON1 rs3917577, CYP3A5 rs15524, COL4A1 rs874204 and PTGIR rs1126510 polymorphisms showed association with CVDs. The miRNA hsa-miR-224-5p showed differential expression in the PON1 rs3917577 GG genotype. The meta-analysis showed the population-specific impact of PON1 rs662 on South Asian and Middle East populations.

A growing number of studies have suggested that genetic variants affecting the micro-RNA- binding mechanisms (miRSNPs) constitute a promising novel class of biomarkers for prostate cancer (PCa) biology. Among the most extensively studied miRSNPs in the context of cancer is the variation rs4245739 in the MDM4 gene, while a recent large-scale analysis revealed significant differences in genotype distributions between aggressive and non-aggressive disease for rs1058205 in KLK3 and rs1010 in VAMP8. In this study, we examined a total of 1083 subjects for these three variants using Taqman® SNP Genotyping Assays. Three hundred and fifty-five samples of peripheral blood were obtained from patients with PCa and 358 samples from patients with benign prostatic hyperplasia (BPH). The control group consisted of 370 healthy volunteers. Comparisons of genotype distributions among PCa and BPH patients, as well as between PCa patients and healthy controls, yielded no evidence of association between the analyzed genetic variants and the risk of developing PCa. However, all three tested genetic variants have shown the association with the parameters of PCa progression. For KLK3 variant rs1058205, minor allele C was found to associate with the lower serum PSA score in PCa patients (PSA > 20 ng/ml vs. PSA < 10 ng/ml comparison, Prec = 0.038; ORrec = 0.20, 95%CI 0.04-1.05). The obtained results point out the potential relevance of the tested genetic variants for the disease aggressiveness assessment.

BACKGROUND: Pharmacogenomics research has concentrated on variation in genes coding for drug metabolizing enzymes, transporters and nuclear receptors. However, variation affecting microRNA could also play a role in drug response. This project set out to investigate potential microRNA target sites in 11 genes and the extent of variation in the 3\'-UTR of six selected genes; CYP1A2, CYP2B6, CYP2D6, CYP3A4, NR1I2, and UGT2B7.
METHODS: Fifteen microRNA target prediction algorithms were used to identify microRNAs predicted to regulate 11 genes. The 3\'-UTR of the 6 genes which topped the list of potential microRNA targets was sequenced in 30 black South Africans. In addition, genetic variants within these genes were investigated for interference with mRNA-microRNA interactions. Potential effects of observed variants were determined using in silico prediction tools.
RESULTS: The 11 genes coding for DMEs, transporters and nuclear receptors were predicted to be targets of microRNAs with CYP2B6, NR1I2 (PXR), CYP3A4, and CYP1A2, interacting with the most microRNAs. The majority of identified genetic variants were predicted to interfere with microRNA regulation. For example, the variant, rs1054190C in NR1I2 was predicted to result in the presence of a binding site for the microRNA miR-1250-5p, while the variant rs1054191G was predicted to result in the absence of a recognition site for miR-371b-3p, miR-4258 and miR-4707-3p. Fifteen of the seventeen, novel variants occurred within microRNA target sequences.
CONCLUSIONS: The 3\'-UTR harbors variation that is likely to influence regulation of specific genes by microRNA. In silico prediction followed by functional validation could aid in decoding the contribution of variation in the 3\'-UTR, to some unexplained heritability that affects drug response. Understanding the specific role of each microRNA may lead to identification of markers for targeted therapy and therefore improve personalized drug treatment.

Micro RNAs are evolutionarily conserved, single stranded molecules of about 22 nucleotides in length and function post-transcriptionally by partial binding (partial complementarity) to the mRNA of genes. Binding of a specific miRNA to its target on an mRNA can inhibit its expression by a variety of mechanisms. Although the most common mechanism is translational repression as a result of miRNA binding to the 3\'UTR of an mRNA, mechanisms involving mRNA degradation and destabilization have also been described. Micro RNAs are currently considered as \"master regulators\" of gene expression. Since a single miRNA can bind and consequently regulate the expression of more than 100 different transcripts it has been estimated that miRNAs may be able to regulate up to 30% of the protein-coding genes in the human genome. As a result, miRNAs receive widespread attention on their potential role in complicated biological processes and multifactorial diseases. In this review we are discussing the biogenesis of miRNAs, their mode of action as well as their role in human diseases through genetic variations on their target sites.