GSTM3 variant is a novel genetic modifier in Brugada syndrome, a disease with risk of sudden cardiac death

BACKGROUND: Brugada syndrome (BrS) is a rare inherited disease causing sudden cardiac death (SCD). Copy number variants (CNVs) can contribute to disease susceptibility, but their role in Brugada syndrome (BrS) is unknown. We aimed to identify a CNV associated with BrS and elucidated its clinical implications. METHODS: We enrolled 335 unrelated BrS patients from 2000 to 2018 in the Taiwanese population. Microarray and exome sequencing were used for discovery phase whereas Sanger sequencing was used for the validation phase. HEK cells and zebrafish were used to characterize the function of the CNV variant. FINDINGS: A copy number deletion of GSTM3 (chr1:109737011-109737301, hg38) containing the eighth exon and the transcription stop codon was observed in 23.9% of BrS patients versus 0.8% of 15,829 controls in Taiwan Biobank (P <0.001), and 0% in gnomAD. Co-segregation analysis showed that the co-segregation rate was 20%. Patch clamp experiments showed that in an oxidative stress environment, GSTM3 down-regulation leads to a significant decrease of cardiac sodium channel current amplitude. Ventricular arrhythmia incidence was significantly greater in gstm3 knockout zebrafish at baseline and after flecainide, but was reduced after quinidine, consistent with clinical observations. BrS patients carrying the GSTM3 deletion had higher rates of sudden cardiac arrest and syncope compared to those without (OR: 3.18 (1.77-5.74), P<0.001;OR: 1.76 (1.02-3.05), P = 0.04, respectively). INTERPRETATION: This GSTM3 deletion is frequently observed in BrS patients and is associated with reduced INa, pointing to this as a novel potential genetic modifier/risk predictor for the development of the electrocardiographic and arrhythmic manifestations of BrS. FUNDING: This work was supported by the Ministry of Science and Technology (107-2314-B-002-261-MY3 to J.M.J. Juang), and by grants HL47678, HL138103 and HL152201 from the National Institutes of Health to CA.

Medical mask versus cotton mask for preventing respiratory droplet transmission in micro environments.

The objective of this study was to investigate whether cotton mask worn by respiratory infection person could suppress respiratory droplet levels compared to medical mask. We recruited adult volunteers with confirmed influenza and suspected cases of coronavirus disease 2019 (COVID-19) to wear medical masks and self-designed triple-layer cotton masks in a regular bedroom and a car with air conditioning. Four 1-hour repeated measurements (two measurements for bedroom the others for car) of particles with a size range of 20-1000 nm measured by number concentrations (NC0.02-1), temperature and relatively humidity, and cough/sneeze counts per hour were conducted for each volunteer. The paired t-tests were used for within-group comparisons in a bedroom and in a car. The results showed that there was no significant difference in NC0.02-1 or cough/sneeze counts between volunteers with medical masks and cotton masks in a bedroom or a car. We concluded that the cotton mask could be a potential substitute for medical mask for respiratory infection person in microenvironment with air conditioning. Healthy people may daily use cotton mask in the community since cotton mask is washable and reusable.