Pharmacogenomics in Asia: a systematic review on current trends and novel discoveries.

While early pharmacogenomic studies have primarily been carried out in Western populations, there has been a notable increase in the number of Asian studies over the past decade. We systematically reviewed all pharmacogenomic studies conducted in Asia published before 2016 to highlight trends and identify research gaps in Asia. We observed that pharmacogenomic research in Asia was dominated by larger developed countries, notably Japan and Korea, and mainly driven by local researchers. Studies were focused on drugs acting on the CNS, chemotherapeutics and anticoagulants. Significantly, several novel pharmacogenomic associations have emerged from Asian studies. These developments are highly encouraging for the strength of regional scientific and clinical community and propound the importance of discovery studies in different populations.

Prevalence and characteristics of adverse drug reactions at admission to hospital: a prospective observational study.

AIMS: Adverse drug reactions (ADRs) contribute to poorer patient outcomes and additional burden to the healthcare system. However, data on the true burden, relevant types and drugs causing ADRs are lacking. The aim of this study was to determine the prevalence of ADR-related hospitalization in the general adult population in Singapore and to investigate their characteristics. METHODS: We prospectively recruited 1000 adult patients with unplanned admission to a large tertiary-care hospital. Two independent reviewers evaluated all suspected ADRs for causality, type, severity and avoidability. The prevalence of ADR-related hospitalization was calculated based on 'definite' and 'probable' ADRs. Logistic regression was used to evaluate predictors for having an ADR at admission. RESULTS: The prevalence of all ADRs at admission was 12.4% (95% CI: 10.5-14.6%) and ADRs causing admission was 8.1% (95% CI: 6.5-10.0%). The most common ADRs were gastrointestinal-related. The most common drug category causing ADRs were cardiovascular drugs. Patients with ADRs had a longer length of stay than those who did not (median 4 vs. 3 days, P = 1.70 × 10-3 ). About 30% of ADRs at admission were caused by at least one drug with a clinical annotation in the Pharmacogenomics KnowledgeBase (PharmGKB), suggesting that some of these ADRs may have been predicted by pharmacogenetic testing. CONCLUSIONS: We have quantified the burden and characteristics of clinically impactful ADRs in the Singaporean general adult population. Our results will provide vital information for efforts in reducing ADRs through targeted vigilance, patient education and pharmacogenomics in Singapore.

Residual Conformational Entropies on the Sugar-Phosphate Backbone of Nucleic Acids: An Analysis of the Nucleosome Core DNA and the Ribosome.

A nucleic acid folds according to its free energy, but persistent residual conformational fluctuations remain along its sugar-phosphate backbone even after secondary and tertiary structures have been assembled, and these residual conformational entropies provide a rigorous lower bound for the folding free energy. We extend a recently reported algorithm to calculate the residual backbone entropy along a RNA or DNA given configuration of its bases and apply it to the crystallographic structures of the 23S ribosomal subunit and DNAs in the nucleosome core particle. In the 23S rRNAs, higher entropic strains are concentrated in helices and certain tertiary interaction platforms while residues with high surface accessibility and those not involved in base pairing generally have lower strains. Upon folding, residual backbone entropy in the 23S subunit accounts for an average free energy penalty of +0.47 (kcal/mol)/nt (nt = nucleotide) at 310 K. In nucleosomal DNAs, backbone entropies show periodic oscillations with sequence position correlating with the superhelical twist and shifts in the base-pair-step geometries, and nucleosome positioning on the bound DNA exerts strong influence over where entropic strains are located. In contrast to rRNAs, residual backbone entropies account for a free energy penalty of only +0.09 (kcal/mol)/nt in duplex relative to single-stranded DNAs.