👤 Quratul Ann

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder associated with extreme hypertriglyceridemia and high risk of acute pancreatitis. Olezarsen-an antisense oligonucleotide targeting hepatic apolipoprotein C3 (APOC3) messenger RNA-reduces triglycerides and may decrease pancreatitis risk. Olezarsen 80 mg once monthly is approved in the United States as an adjunct to diet to reduce triglycerides in adults with FCS. To assess the effect of olezarsen on all-cause healthcare resource utilization (HCRU) and overall experience of patients with genetically identified FCS enrolled in the Balance trial (NCT04568434). Prespecified exploratory endpoints included yearly all-cause hospitalization, total inpatient days, and emergency room visits for patients treated with olezarsen (80 or 50 mg) vs placebo, as well as Patient Global Impression of Change (PGIC). Ad hoc outcomes included length of hospital stay, intensive care unit (ICU) admissions, reasons for HCRU, and all-cause HCRU according to patients' history of acute pancreatitis and for individual olezarsen doses vs placebo. Treatment with olezarsen vs placebo for 1 year was associated with an 84% reduction in all-cause hospitalizations (mean rate ratio [95% CI], 0.16 [0.05, 0.50]), 6.3 fewer total inpatient days (95% CI, -11.09, -1.53), better PGIC scores, shorter length of stay, and numerically fewer ICU admissions. Acute pancreatitis was the most frequent cause of hospitalization. Reduction in all-cause inpatient service utilization was consistent for individual dose groups and in patients with a history of acute pancreatitis. In the Balance study, olezarsen reduced all-cause inpatient service utilization and improved the experience of patients with FCS. Show less

The concentration of high-density lipoprotein-cholesterol (HDL-C) in humans is partially determined by genetic factors; however, the role of these factors is incompletely understood. The aim of this study was to examine the prevalence and characteristics of CETP, LIPC, and SCARB1 variants in Korean individuals with extremely high HDL-C levels. We also analysed associations between these variants and cholesterol efflux capacity (CEC), reactive oxygen species (ROS) generation, and vascular cell adhesion molecule-1 (VCAM-1) expression. Of 13,545 participants in the cardiovascular genome cohort, 42 subjects with HDL-C levels >100 mg/dL were analysed. The three target genes were sequenced by targeted next-generation sequencing, the functional effects of detected variants were predicted, and CEC was assessed using a radioisotope and apolipoprotein B-depleted sera. We observed two rare variants of CETP in 13 individuals (rare variant c.A1196G [p.D399G] of CETP was discovered in 12 subjects) and one rare variant of SCARB1 in one individual. Furthermore, all subjects had at least one of four common variants (one CETP and three LIPC variants). Two additional novel CETP variants of unknown frequency were found in two subjects. However, the identified variants did not show significant associations with CEC, ROS generation, or VCAM-1 expression. Our study provides additional insights into the role of genetics in individuals with extremely high HDL-C. Show less

Members of the heterochromatin protein 1 family (HP1α, β and γ) are mostly associated with heterochromatin and play important roles in gene regulation and DNA damage response. Altered expression of individual HP1 subtype has profound impacts on cell proliferation and tumorigenesis. We analyzed the expression profile of HP1 family by data mining using a published microarray data set coupled with retrospective immunohistochemistry analyses of archived breast cancer biospecimens. We found that the patient group overexpressing HP1β mRNA is associated with poorly differentiated breast tumors and with a significantly lower survival rate. Immunohistochemical staining against HP1α, HP1β and HP1γ shows that respective HP1 expression level is frequently altered in breast cancers. 57.4-60.1% of samples examined showed high HP1β expression and 39.9-42.6 % of examined tumors showed no or low expression of each HP1 subtype. Interestingly, comparative analysis on HP1 expression profile and breast cancer markers revealed a positive correlation between the respective expression level of all three HP1 subtypes and Ki-67, a cell proliferation and well-known breast cancer marker. To explore the effect of individual HP1 on PARP inhibitor therapy for breast cancer, MCF7 breast cancer cells and individually HP1-depleted MCF7 cells were treated with PARP inhibitor ABT-888 with or without carboplatin. Notably, HP1β-knockdown cells are hypersensitive to the PARP inhibitor ABT-888 alone and its combination with carboplatin. In summary, while increased HP1β expression is associated with the poor prognosis in breast cancer, compromised HP1β abundance may serve as a useful predictive marker for chemotherapy, including PARP inhibitors against breast cancer. Show less