Identification of Potential Biological Factors Affecting the Treatment of Ticagrelor After Percutaneous Coronary Intervention in the Chinese Population.

BACKGROUND: Generally, many individual factors can affect the clinical application of drugs, of which genetic factors contribute more than 20%. Ticagrelor is a new class of receptor inhibitors receptor antagonist of P2Y12 and is used as an antiplatelet agents. But it is not affected by the influence of CYP2C19 polymorphism. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of ticagrelor in the antiplatelet efficacy and safety, through pharmacogenomics research. METHODS: Whole-exome sequencing (WES) was performed in 100 patients after PCI with ticagrelor treatment. Clinical characteristics and WES of patients were used to performed genome-wide association analysis (GWAS), region-based tests of rare DNA variant to find the influencing factors of antiplatelet effect to ticagrelor and bleeding events. Co-expression, protein-protein interaction (PPI) network and pathway enrichment analysis were then used to find possible genetic mechanisms. Atlas of GWAS (https://atlas.ctglab.nl/) were used for external data validation. RESULTS: DNAH17, PGS1 and ABCA1 as the potential variant genes are associated with the expected antiplatelet effect to ticagrelor. The affected pathways may include the synthesis and metabolism of lipoprotein cholesterol and the catabolic process of pyrimidine-containing compound (GO:0072529). Age, sex and PLT were found may be potential factors for ticagrelor bleeding events. CONCLUSION: We systematically identified new genetic variants and some risk factors for reduced efficacy of ticagrelor and highlighted related genes that may be involved in antiplatelet effects and bleeding event of ticagrelor. Our results enhance the understanding of the absorption and metabolic mechanisms that influence antiplatelet response to ticagrelor treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03161002. First Posted: May 19, 2017. https://clinicaltrials.gov/ct2/show/study/NCT03161002.

Effects of warming on ectomycorrhizal colonization and nitrogen nutrition of Picea asperata seedlings grown in two contrasting forest ecosystems.

Ectomycorrhiza (ECM) plays an important role in plant nitrogen (N) nutrition and regulates plant responded to climate warming. We conducted a field experiment in a natural forest and a plantation in the eastern Tibetan Plateau to estimate the warming effects of open-top chambers (OTC) on ECM and N nutrition of Picea asperata seedlings. Four-year warming significantly decreased ECM colonization, ECM fungal biomass, fine root vigor, and the N concentration of leaf, stem and coarse root, but significantly increased fine root N concentration and N content of leaf, stem, fine root and whole plant in natural forest. Contrarily, warming induced no obvious change in most of these parameters in plantation. Moreover, warming decreased rhizospheric soil inorganic N content in both forests. Our results showed that four-year warming was not beneficial for ECM colonization of P. asperata seedlings in the two forests, and the seedlings in natural forest were more sensitive and flexible to experimental warming than in plantation. The changes of ECM colonization and fine root biomass for effective N uptake would be good for plant growth and remit N leaching under future warming in natural forest.