ATP-Binding Cassette Transporter A1 Deficiency in Human Induced Pluripotent Stem Cell-Derived Hepatocytes Abrogates HDL Biogenesis and Enhances Triglyceride Secretion.

Despite the recognized role of the ATP-binding Cassette Transporter A1 (ABCA1) in high-density lipoprotein (HDL) metabolism, our understanding of ABCA1 deficiency in human hepatocytes is limited. To define the functional effects of human hepatocyte ABCA1 deficiency, we generated induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from Tangier disease (TD) and matched control subjects. Control HLCs exhibited robust cholesterol efflux to apolipoprotein A-I (apoA-I) and formed nascent HDL particles.

Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans.

Fever predicts clinical outcomes in sepsis, trauma and during cardiovascular stress, yet the genetic determinants are poorly understood. We used an integrative genomics approach to identify novel genomic determinants of the febrile response to experimental endotoxemia. We highlight multiple integrated lines of evidence establishing the clinical relevance of this novel fever locus.

Translational studies of lipoprotein-associated phospholipase A₂ in inflammation and atherosclerosis.

Objectives: This study sought to examine the role of lipoprotein-associated phospholipase A₂ (Lp-PLA₂/PLA2G7) in human inflammation and coronary atherosclerosis.

Background: Lp-PLA₂ has emerged as a potential therapeutic target in coronary heart disease. Data supporting Lp-PLA₂ are indirect and confounded by species differences; whether Lp-PLA₂ is causal in coronary heart disease remains in question.

Mining the LIPG allelic spectrum reveals the contribution of rare and common regulatory variants to HDL cholesterol.

Genome-wide association studies (GWAS) have successfully identified loci associated with quantitative traits, such as blood lipids. Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci. The goal of these studies is to identify causative variants and missing heritability, including heritability due to low frequency and rare alleles with large phenotypic impact.

Dense genotyping of candidate gene loci identifies variants associated with high-density lipoprotein cholesterol.

Background: Plasma levels of high-density lipoprotein cholesterol (HDL-C) are known to be heritable, but only a fraction of the heritability is explained. We used a high-density genotyping array containing single-nucleotide polymorphisms (SNPs) from HDL-C candidate genes selected on known biology of HDL-C metabolism, mouse genetic studies, and human genetic association studies. SNP selection was based on tagging SNPs and included low-frequency nonsynonymous SNPs.