PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis.

Moderate-to-severe psoriasis (Ps) treatment includes systemic drugs and biological agents. Apremilast, a small molecule primarily metabolized by cytochrome CYP3A4, modulates the immune system by specifically inhibiting phosphodiesterase type 4 (PDE4) isoforms and is currently used for the treatment of Ps and psoriatic arthritis (PsA). Clinical trials and real-world data showed variable efficacy in response among Ps patients underlying the need for personalized therapy. This study implements a candidate-gene and a network-based approach to identify genetic markers associated with apremilast response in forty-nine Greek Ps patients. Our data revealed an association of sixty-four SNPs within or near PDE4 and CYP3A4 genes, four SNPs in ncRNAs ANRIL, LINC00941 and miR4706, which influence the abundance or function of PDE4s, and thirty-three SNPs within fourteen genes whose protein products either interact directly with PDE4 proteins or constitute components of the cAMP signaling pathway which is modulated by PDE4s. Notably, fifty-six of the aforementioned SNPs constitute eQTLs for the respective genes in relevant to psoriasis tissues/cells implying that these variants could be causal. Our analysis provides a number of novel genetic variants that, upon validation in larger cohorts, could be utilized as predictive markers regarding the response of Ps patients to apremilast treatment.

A critical approach for successful use of circulating microRNAs as biomarkers in cardiovascular diseases: the case of hypertrophic cardiomyopathy.

MicroRNAs (miRNAs) are small noncoding RNA molecules that act as major regulators of gene expression at the post-transcriptional level. As the potential applications of miRNAs in the diagnosis and treatment of human diseases have become more evident, many studies of hypertrophic cardiomyopathy (HCM) have focused on the systemic identification and quantification of miRNAs in biofluids and myocardial tissues. HCM is a hereditary cardiomyopathy caused by mutations in genes encoding proteins of the sarcomere. Despite overall improvements in survival, progression to heart failure, stroke, and sudden cardiac death remain prominent features of living with HCM. Several miRNAs have been shown to be promising biomarkers of HCM; however, there are many challenges to ensuring the validity, consistency, and reproducibility of these biomarkers for clinical use. In particular, miRNA testing may be limited by pre-analytical and analytical caveats, making our interpretation of results challenging. Such factors that may affect miRNA testing include sample type selection, hemolysis, platelet activation, and renal dysfunction. Therefore, researchers should be careful when developing appropriate standards for the design of miRNA profiling studies in order to ensure that all results provided are both accurate and reliable. In this review, we discuss the application of miRNAs as biomarkers for HCM.