Dataset Information

Functional variants of TIM-3/HAVCR2 3'UTR in lymphoblastoid cell lines.

ABSTRACT: Aim:Variants of TIM-3/HAVCR2 3'UTR miRNA binding sites are significantly associated with cancer; however, roles in post-transcriptional regulation have not been elucidated. Methods:The regulatory and coding region single nucleotide polymorphisms (SNPs) of TIM-3/HAVCR2 were identified using an online database. Single nucleotide polymorphism Function Prediction was used to predict potential functional relevance of miRNA binding sites. Results:The analysis indicated rs9313439, rs4704846, rs3087616 and rs1036199 affect possible miRNA binding sites in TIM-3/HAVCR2 3'UTR. We used additional data on genotypes and limited minor allele frequency >5% in the HapMap populations. Only rs3087616 and rs4704846 were significantly associated with TIM-3/HAVCR2. Conclusion:Both rs3087616 and rs4704846 could be putative variants mediating post-transcriptional regulation of the TIM-3/HAVCR2. Deeper understanding of how 3'UTR variants influence the activity by TIM-3/HAVCR2 for therapy against cancer.

SUBMITTER: Pu F

PROVIDER: S-EPMC5961449 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Functional variants of <i>TIM-3/HAVCR2</i> 3'UTR in lymphoblastoid cell lines.

Pu Feifei F Pu Feifei F Chen Fengxia F Zhang Zhicai Z Feng Jing J Xia Ping P

Future science OA 20180315 5

<h4>Aim</h4>Variants of <i>TIM-3/HAVCR2</i> 3'UTR miRNA binding sites are significantly associated with cancer; however, roles in post-transcriptional regulation have not been elucidated.<h4>Methods</h4>The regulatory and coding region single nucleotide polymorphisms (SNPs) of <i>TIM-3/HAVCR2</i> were identified using an online database. Single nucleotide polymorphism Function Prediction was used to predict potential functional relevance of miRNA binding sites.<h4>Results</h4>The analysis indica ...[more]

PMID: 29796301

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Project description:BackgroundStatins are widely prescribed to lower plasma low-density lipoprotein cholesterol levels. Though statins reduce cardiovascular disease risk overall, statin efficacy varies, and some people experience adverse side effects while on statin treatment. Statins also have pleiotropic effects not directly related to their cholesterol-lowering properties, but the mechanisms are not well understood. To identify potential genetic modulators of clinical statin response, we looked for genetic variants associated with statin-induced changes in gene expression (differential eQTLs or deQTLs) in lymphoblastoid cell lines (LCLs) derived from participants of the Cholesterol and Pharmacogenetics (CAP) 40 mg/day 6-week simvastatin clinical trial. We exposed CAP LCLs to 2 μM simvastatin or control buffer for 24 h and performed polyA-selected, strand-specific RNA-seq. Statin-induced changes in gene expression from 259 European ancestry or 153 African American ancestry LCLs were adjusted for potential confounders prior to association with genotyped and imputed genetic variants within 1 Mb of each gene's transcription start site.ResultsFrom the deQTL meta-analysis of the two ancestral populations, we identified significant cis-deQTLs for 15 genes (TBC1D4, MDGA1, CHI3L2, OAS1, GATM, ASNSD1, GLUL, TDRD12, PPIP5K2, OAS3, SERPINB1, ANKDD1A, DTD1, CYFIP2, and GSDME), eight of which were significant in at least one of the ancestry subsets alone. We also conducted eQTL analyses of the endogenous (control-treated), statin-treated, and average of endogenous and statin-treated LCL gene expression levels. We identified eQTLs for approximately 6000 genes in each of the three (endogenous, statin-treated, and average) eQTL meta-analyses, with smaller numbers identified in the ancestral subsets alone.ConclusionsSeveral of the genes in which we identified deQTLs have functions in human health and disease, such as defense from viruses, glucose regulation, and response to chemotherapy drugs. This suggests that DNA variation may play a role in statin effects on various health outcomes. These findings could prove useful to future studies aiming to assess benefit versus risk of statin treatment using individual genetic profiles.

Dataset Information

Functional variants of TIM-3/HAVCR2 3'UTR in lymphoblastoid cell lines.

Publications

Functional variants of <i>TIM-3/HAVCR2</i> 3'UTR in lymphoblastoid cell lines.

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