Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritisation

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy

The Asthma-associated PER1-like domain-containing protein 1 (PERLD1) Haplotype Influences Soluble Glycosylphosphatidylinositol Anchor Protein (sGPI-AP) Levels in Serum and Immune Cell Proliferation

10.1038/s41598-020-57592-9Scientific Reports10171

The protection of Anthrodia camphorata against acute hepatotoxicity of alcohol in rats

Antrodia camphorata is a unique mushroom of Taiwan and has been used as a folk medicine for protection against liver damage induced by alcohol intoxication. However, no report has been presented in this respect. In this rat study, we examined whether the mycelium and sporocarp of Antrodia camphorata protect against acute liver damage induced by ethanol (EtOH). Rats were orally administered with mycelium and sporocarp of Antrodia camphorata for 9 days before EtOH challenge (5.5 g/kg body wt., i.p.). Rats were divided into eight groups (A-H) and except for groups A and H, all rats were injected with alcohol. A: Control; B: EtOH control: C: Silymarin (250 mg/kg bw., p.o.); D: 0.5 g mycelium/kg; E: 1.0 g mycelium/kg; F: 0.5 g sporocarp/kg; G: 1.0 g sporocarp/kg; and H: 1.0 g mycelium/kg. The results showed that EtOH administration markedly increased the activities of glutamate-pyruvate aminotransferase (GPT) and glutamate-oxaloacetate aminotransferase (GOT). Both mycelium and sporocarp of Antrodia camphorata significantly decreased the activity of GOT and GPT, but the effects were not dose-dependent. Mycelium and sporocarp of Antrodia camphorata also significantly and dose-dependently decreased lipid peroxidation (measured as TBARS) induced by EtOH. EtOH treatment significantly increased the activities of hepatic superoxide dismutase (SOD) and catalase, but did not significantly affect the activity of glutathione peroxidase. Pre-treatment with either the mycelium or the sporocarp completely prevented the rise in the activity of SOD and catalase. The histopathological examination revealed that both mycelium and sporocarp markedly protected against lipid vacuole accumulation and hydropic degeneration of hepatocytes induced by EtOH. Thus, the present results demonstrated that both mycelium and sporocarp of Antrodia camphorata protect against acute liver damage induced by EtOH. In addition, rats fed 1.0 g mycelium without EtOH treatment produced no observable toxicity during the experimental period

Association of bronchial steroid inducible methylation quantitative trait loci with asthma and chronic obstructive pulmonary disease treatment response.

Pathogenesis and treatment of chronic pulmonary disease

Correction: Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritization (The Pharmacogenomics Journal, (2020), 10.1038/s41397-019-0140-y)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Multi-ancestry genome-wide association study of asthma exacerbations.

BACKGROUND: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. METHODS: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10-5 ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. RESULTS: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (ORT allele ) = 0.82, p = 9.05 × 10-6 and replication: ORT allele  = 0.89, p = 5.35 × 10-3 ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele  = 0.85, p = 3.10 × 10-5 and replication: ORC allele  = 0.89, p = 1.30 × 10-2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. CONCLUSIONS: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense