A Very Low-Carbohydrate Program in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease and Phospholipase Domain-Containing Protein 3 Risk Genotype: Pre-Post Intervention Study.

Background: Insulin resistance and the G allele of rs738409 interact to create a greater risk of metabolic dysfunction-associated steatotic liver disease.

Objective: This study aims to confirm that one promising way to reduce insulin resistance is by following a very low-carbohydrate (VLC) dietary pattern.

Methods: Adults with rs738409-GG or -CG with liver steatosis and elevated liver function tests, were taught an ad libitum VLC diet, positive affect and mindful eating skills, goal setting, and self-monitoring and given feedback and coaching for 4 months.

PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 30% of Western populations. While obesity is a recognized risk factor, MASLD does not develop in all obese individuals, highlighting the need to understand genetic and environmental interactions. The PNPLA3 I148M variant has been identified as a key genetic risk factor, significantly increasing the likelihood of MASLD development and progression.

TM6SF2 -rs58542926 Genotype Has Opposing Effects on Incidence of Hepatic and Cardiac Events in a Community Cohort.

Introduction: TM6SF2 -rs58542926-T is associated with increased cirrhosis and modestly decreased coronary artery disease prevalence. However, relative effects of TM6SF2 genotype on major adverse cardiovascular events (MACE) vs liver-related events (LRE) are not known.

Methods: We used the UK Biobank, a prospective cohort with genetic and inpatient diagnosis data.

Genetic insight into the relationship between inflammatory bowel disease and infection.

Patients with inflammatory bowel disease (IBD) are at increased risk of infection (CDI). Herein, we aimed to determine if genetic risk contributes to this observed association. We carried out a genome-wide association study (GWAS) analysis in the Michigan Genomics Initiative and the United Kingdom Biobank for CDI based on ICD codes and meta-analyzed these results with similar publicly accessible GWAS summary statistics from Finngen.

Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening.

An elevated level of lipoprotein(a), or Lp(a), in the bloodstream has been causally linked to the development of atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Steady state levels of circulating lipoproteins are modulated by their rate of clearance, but the identity of the Lp(a) uptake receptor(s) has been controversial. In this study, we performed a genome-scale CRISPR screen to functionally interrogate all potential Lp(a) uptake regulators in HuH7 cells.