No abstract

Aim: GDF15 levels are a biomarker for metformin use. We performed the functional annotation of noncoding genome-wide association study (GWAS) SNPs for GDF15 levels and the Genotype-Tissue Expression (GTEx)-expression quantitative trait loci (eQTLs) for GDF15 expression within metformin-activated enhancers around GDF15. Materials & methods: These enhancers were identified using chromatin immunoprecipitation followed by sequencing data for active (H3K27ac) and silenced (H3K27me3) histone marks on human hepatocytes treated with metformin, Encyclopedia of DNA Elements data and cis-regulatory elements assignment tools. Results: The GWAS lead SNP rs888663, the SNP rs62122429 associated with GDF15 levels in the Outcome Reduction with Initial Glargine Intervention trial, and the GTEx-expression quantitative trait locus rs4808791 for GDF15 expression in whole blood are located in a metformin-activated enhancer upstream of GDF15 and tightly linked in Europeans and East Asians. Conclusion: Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels.

No abstract

No abstract

The immune system responds to infection or vaccination through a dynamic and complex process that involves several molecular and cellular factors. Among these factors, long non-coding RNAs (lncRNAs) have emerged as significant players in all areas of biology, particularly in immunology. Most of the mammalian genome is transcribed in a highly regulated manner, generating a diversity of lncRNAs that impact the differentiation and activation of immune cells and affect innate and adaptive immunity. Here, we have reviewed the range of functions and mechanisms of lncRNAs in response to infectious disease, including pathogen recognition, interferon (IFN) response, and inflammation. We describe examples of lncRNAs exploited by pathogenic agents during infection, which indicate that lncRNAs are a fundamental part of the arms race between hosts and pathogens. We also discuss lncRNAs potentially implicated in vaccine-induced immunity and present examples of lncRNAs associated with the antibody response of subjects receiving Influenza or Yellow Fever vaccines. Elucidating the widespread involvement of lncRNAs in the immune system will improve our understanding of the factors affecting immune response to different pathogenic agents, to better prevent and treat disease.