A5082697278- Lipoproteins and Cardiovascular Health
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cholesterol and Lipid Metabolism
- Lipid metabolism and disorders
- Cancer, Lipids, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Genetic Associations and Epidemiology
- Liver Disease Diagnosis and Treatment
- Pharmacogenetics and Drug Metabolism
- Sleep and related disorders
- Caveolin-1 and cellular processes
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Fatty Acid Research and Health
- Drug Transport and Resistance Mechanisms
- Sleep and Wakefulness Research
- Protease and Inhibitor Mechanisms
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Regulation of Appetite and Obesity
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Restless Legs Syndrome Research
- Atherosclerosis and Cardiovascular Diseases
- Circadian rhythm and melatonin
University of California, San Francisco
2016-2025
Cardiovascular Institute Hospital
1997-2015
Hartford Hospital
2014
Genomas (United States)
2014
Hartford Financial Services (United States)
2014
Center for Human Genetics
2008
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
2008
University of California, Los Angeles
1997-2008
Maastricht University Medical Centre
2008
Kuopio University Hospital
2008
A genome-wide association study was performed to identify genetic factors involved in susceptibility psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin joints humans. 223 PS cases (including 91 with PSA) were genotyped 311,398 single nucleotide polymorphisms (SNPs), results compared those from 519 Northern European controls. Replications an independent cohort 577 737 controls U.S., 576 PSA patients 480 U.K.. Strongest associations class I region major...
Bile acid synthesis plays a critical role in the maintenance of mammalian cholesterol homeostasis. The CYP7A1 gene encodes enzyme 7alpha-hydroxylase, which catalyzes initial step catabolism and bile synthesis. We report here new metabolic disorder presenting with hyperlipidemia caused by homozygous deletion mutation CYP7A1. leads to frameshift (L413fsX414) that results loss active site function. High levels LDL were seen three subjects. Analysis liver biopsy stool from one these subjects...
Bile acid synthesis plays a critical role in the maintenance of mammalian cholesterol homeostasis. The CYP7A1 gene encodes enzyme 7α-hydroxylase, which catalyzes initial step catabolism and bile synthesis. We report here new metabolic disorder presenting with hyperlipidemia caused by homozygous deletion mutation CYP7A1. leads to frameshift (L413fsX414) that results loss active site function. High levels LDL were seen three subjects. Analysis liver biopsy stool from one these subjects...
The objective of this study was to establish conditions whereby apoB secreted from HepG2 cells could be regulated over a wide range, and determine whether changes output were correlated with the level mRNA. presence oleate (complexed 3% albumin at molar ratio 1.7:1) resulted in 3.5-fold stimulation secretion that apparent after only 3 h. Insulin halved rate inhibition detectable within physiological insulin but not until 12-16 Albumin culture medium had dose-dependent inhibitory effect on...
•Severe hypertriglyceridemia has a strong genetic basis.•Almost all of those with genetically identified factors had polygenic hypertriglyceridemia.•Biallelic (ie, homozygous or compound heterozygous) variants were infrequent.•The accumulation common was the most predominant determinant. BackgroundHypertriglyceridemia (HTG) is complex trait defined by elevated plasma triglyceride levels. Genetic determinants HTG have so far been examined in piecemeal manner; understanding its molecular...
A number of chronic diseases, including cardiovascular disease, appear to have a multifactorial genetic risk component. Consequently, techniques are needed facilitate evaluation complex factors in large cohorts. We designed prototype assay for genotyping panel 35 biallelic sites that represent variation within 15 genes from biochemical pathways implicated the development and progression disease. Each DNA sample is amplified using two multiplex polymerase chain reactions, alleles genotyped...
Detection of new ligand-defective mutations apolipoprotein B (apoB) will enable identification sequences involved in binding to the LDL receptor. Genomic DNA from patients attending a lipid clinic was screened by single-strand conformation polymorphism analysis for novel putative receptor-binding domain apoB-100. A 46-yr-old woman Celtic and Native American ancestry with primary hypercholesterolemia (total cholesterol [TC] 343 mg/dl; [LDL-C] 241 mg/dl) pronounced peripheral vascular disease...
The purpose of this study was to identify genetic variants associated with severe coronary artery disease (CAD).We used 3 case-control studies white subjects whose severity CAD assessed by angiography. first 2 were generate hypotheses that then tested in the third study. We 12,077 putative functional single nucleotide polymorphisms (SNPs) Study 1 (781 cases, 603 controls) and identified 302 SNPs nominally CAD. Testing these (471 298 controls), we found 5 (in LPA, CALM1, HAP1, AP3B1, ABCG2)...
A protein that is expressed on capillary endothelial cells, called GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding 1), binds lipase and shuttles it to its site of action in the lumen. deficiency prevents from reaching Patients with have low plasma levels lipase, impaired intravascular hydrolysis triglycerides, severe hypertriglyceridemia (chylomicronemia). During characterization a monoclonal antibody-based immunoassay for GPIHBP1, we encountered two samples...
Truncating mutations in the giant sarcomeric protein Titin result dilated cardiomyopathy and skeletal myopathy. The most severely affected patients harbor truncations C-terminal two-thirds of protein, suggesting that mutation position might influence disease mechanism. Using CRISPR/Cas9 technology, we generated six zebrafish lines with N-terminal regions. Although all exons were constitutive, caused severe myopathy whereas demonstrated mild phenotypes. Surprisingly, neither type acted as a...
Functionally significant heterozygous mutations in the Melanocortin-4 receptor (MC4R) have been implicated 2.5% of early onset obesity cases European cohorts. The role this gene severely obese adults, particularly smaller North American patient cohorts, has less convincing. More recently, it proposed that a phylogenetically and physiologically related receptor, Melanocortin-3 (MC3R), could also be cause severe human obesity. objectives study were to determine if impairing function MC4R or...
Studies suggest that people living with HIV (PLWH) experience many unrelieved symptoms. The purpose of this study was to estimate the occurrence pain in adult PLWH and determine whether participants differed from those without on selected demographic factors, clinical characteristics, symptoms fatigue, sleep disturbance, anxiety, or depression. authors conducted a descriptive, comparative, correlational 317 seen at academic community clinics San Francisco. Participants completed...
Whether patients who subsequently develop early postoperative delirium have a genetic predisposition that renders them at risk for has not been determined.The authors conducted nested cohort study to include aged > or = 65 yr were scheduled undergo major noncardiac surgery requiring anesthesia. A structured interview was preoperatively and the first 2 days postoperatively determine presence of delirium, defined using Confusion Assessment Method. Blood drawn measurement apolipoprotein...
Objective: To characterize specifi c types of sleep problems experienced by adults with HIV.Method: The design was cross-sectional involving questionnaires, diaries, and wrist actigraphy.The convenience sample included 290 living HIV, 22-77 years age.Measures self-report for onset latency, actigraphy estimates total time at night, wake after onset, daytime sleep.Results: Nearly half (45%) the slept < 6 h per night.Diffi culty falling asleep reported 34%, 56% had fragmented according to...
The identification of a patient with rare form severe dysbetalipoproteinemia allowed the study consequences total absence apolipoprotein E (apoE).To discover molecular basis this disorder and to determine effects complete apoE on neurocognitive visual function lipoprotein metabolism.Whole-exome sequencing was performed patient's DNA. He underwent detailed neurological testing analysis. Lipoprotein analysis also in Cardiovascular Research Institute, University California, San Francisco, blood...
Previously we identified and cloned the cDNA for a new protein, apolipoprotein L (apoL), present in plasma mainly associated with large high density lipoprotein particles. Using 5′ rapid amplification of ends, RT-PCR comparison three Human Genome Project expressed sequence tag sequences, have characterized gene apoL additional, highly homologous proteins that constitute family display no homology previously described apolipoproteins. The genes all four proteins, apoL-I, apoL-II, apoL-III,...
Recent discovery and characterization of APOAV suggests a role in metabolism triglyceride (TG)-rich lipoproteins. Previously, variation at the locus was shown to modestly influence plasma TGs normolipidemic samples. The aims this study were assess effects polymorphism (T-1131C) terms its frequency among three dyslipidemic populations control population, differences allele across available ethnic groups, associations with specific lipoprotein TG cholesterol compartments. We found striking...