A5083501945- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Cancer Genomics and Diagnostics
- Renal Diseases and Glomerulopathies
- Cancer, Lipids, and Metabolism
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Diet, Metabolism, and Disease
- Sphingolipid Metabolism and Signaling
- Genetic factors in colorectal cancer
- Regulation of Appetite and Obesity
- Viral Infections and Vectors
- Genomics and Rare Diseases
- Erythrocyte Function and Pathophysiology
- Advanced Chemical Sensor Technologies
- Prenatal Screening and Diagnostics
- Blood groups and transfusion
- Pregnancy and preeclampsia studies
- Genetic Associations and Epidemiology
- Biochemical Analysis and Sensing Techniques
- Adipose Tissue and Metabolism
- Complement system in diseases
Merck & Co., Inc., Rahway, NJ, USA (United States)
2025
Washington University in St. Louis
2012-2024
Atkins (United States)
2015
Center for Human Genetics
2008
University of Missouri
2001-2002
The precise orosensory inputs engaged for dietary lipids detection in humans are unknown. We evaluated whether a common single nucleotide polymorphism (rs1761667) the CD36 gene that reduces expression and addition of orlistat, lipase inhibitor, to reduce FA release from triacylglycerols (TGs), main component fats, would attenuate fat sensitivity humans. Twenty-one obese subjects with different rs1761667 genotypes (6 AA, 7 AG, 8 GG) were studied on two occasions which oleic acid triolein...
Variants in hepatocyte nuclear factor-4α (HNF4α), a transcription factor that influences the expression of glucose metabolic genes, have been correlated with maturity-onset diabetes young, monogenic form diabetes. Previously, genome scan Ashkenazi Jewish type 2 diabetic families, we observed linkage to chromosome 20q region encompassing HNF4α. Here, haplotype-tag single nucleotide polymorphisms (htSNPs) were identified across 78-kb around HNF4α and evaluated an association analysis (n = 275)...
A region along chromosome 7q was recently linked to components of the metabolic syndrome (MetS) in several genome-wide linkage studies. Within this region, CD36 gene, which encodes a membrane receptor for long-chain fatty acids and lipoproteins, is potentially important candidate. has been documented play an role acid metabolism vivo subsequently may be involved etiology MetS. The protein also impacts survival malaria influence natural selection resulted high genetic variability populations...
Membrane CD36 functions in the uptake of fatty acids (FAs), oxidized lipoproteins and signal transduction after binding these ligands. In rodents, is implicated abnormal lipid metabolism, inflammation atherosclerosis. humans, variants have been identified to influence free FA high-density lipoprotein (HDL) levels associate with risk metabolic syndrome, coronary artery disease stroke. this study, 15 common lipid-associated single nucleotide polymorphisms (SNPs) were evaluated for impact on...
Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear (MT-nDNA). In CHARGEmtDNA+ Consortium, we studied associations mtDNA MT-nDNA with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation imputation variants was followed single-variant gene-based...
Hepatocyte nuclear factor (HNF)-4α is part of a transcription network that key for the development and function β-cell. Rare mutations in HNF4α gene cause maturity-onset diabetes young. A number type 2 linkage studies have found evidence to 20q12–13.1 where located. Two recent an association between four common variants alternative P2 promoter region diabetes. These are strong disequilibrium, minor alleles define one risk haplotype. In both studies, haplotype explained large proportion...
In humans, the A1 (T) allele of dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous nonselective for D2R, leaving relationship between genotype D2R specific binding uncertain. Using positron emission tomography (PET) radioligand, (N-[(11)...
Abstract Background Clesrovimab is a half-life extended RSV-neutralizing antibody targeting site IV of the RSV fusion protein, that currently in phase 3 development for prevention infants. As viral sequences drift over time, possibility emergence resistance exists, and conduct contemporary global surveillance important. Methods Here, we report frequency naturally occurring F gene polymorphisms clesrovimab binding [amino acids (a.a) 426-447] using two approaches. First, total 15,527 protein...
Abstract MK-6194, an interleukin-2 mutein designed to selectively activate regulatory T cells (Tregs), was evaluated for safety, pharmacokinetics (PK), immunogenicity, and pharmacodynamics in healthy participants. In a single ascending dose trial (N = 56), participants received subcutaneous MK-6194 or placebo (3:1 ratio) across levels ranging from 1 10 mg. multiple 54), at 0.5 5 mg every 2 wk (total 3 doses) as well 4 doses). Baseline characteristics were comparable between trials, with...
Single nucleotide polymorphism (SNP) association studies searching for differences in allele frequencies between cases and controls have been widely used genetic analysis. Individual genotyping is prohibitively expensive large sample sizes. Pooling of samples provides the obvious advantage higher throughput lower cost. Here we report our results with analysis SNP DNA pools using PyrosequencingTM technology. For seven different SNPs, observed a mean difference 1.1 ± 0.6% determined two (n =...
Single nucleotide polymorphisms (SNPs) within the hepatocyte nuclear factor 4alpha (HNF4alpha) gene are associated with type 2 diabetes in Finns and Ashkenazi Jews. Previous studies both populations have reported linkage to near HNF4alpha locus on chromosome 20q12-13. To investigate whether is a susceptibility Pima Indians, population highest prevalence of but no evidence for disease 20q, 19 SNPs across promoter coding region were genotyped association analysis. In group 1,037 Indians (573...
Fatty acid (FA) metabolism is tightly regulated across several tissues and impacts insulin sensitivity. CD36 facilitates cellular FA uptake, genetic variants associate with lipid abnormalities susceptibility to metabolic syndrome. The objective of this study was gain insight regarding the in vivo influence muscle adipose tissue CD36. For this, we determined relationships between alternative transcripts, which can reflect tissue-specific regulation, measures resistance.The relative abundance...
Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk metabolic syndrome, but their impact on postprandial lipids, an independent factor for cardiovascular disease, is unclear. We determined the effects SNPs within a ∼410 kb region encompassing CD36 its proximal distal promoters chylomicron (CM) remnants LDL particles at 3.5 6 h following high-fat meal (Genetics Lipid Lowering Drugs Diet Network study, n = 1,117). Five promoter associated with CMs, four delayed TG...
Context: The scavenger receptor CD36 influences the endothelial nitric oxide-cGMP pathway in vitro. Genetic variants that alter level are common African Americans (AAs), a population at high risk of dysfunction. Objective: To examine if minor allele (G) coding variant rs3211938 (G/T) which reduces by approximately 50% function, insulin sensitivity (IS), and response to treatment with potentiator sildenafil. Design: IS (frequently sampled iv glucose tolerance) function (flow mediated dilation...
Genetic testing has uncovered rare variants in complement proteins associated with thrombotic microangiopathy (TMA) and C3 glomerulopathy (C3G). Approximately 50% are classified as of uncertain significance (VUS). Clinical risk assessment patients carrying a VUS remains challenging primarily due to lack functional information, especially the context multiple confounding factors setting kidney transplantation. Our objective was evaluate clinicopathologic genetic TMA C3G transplant cohort. We...
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) characterized by the triad of microangiopathic anemia, thrombocytopenia, and acute kidney injury (AKI).1Goodship T.H. Cook H.T. Fakhouri F. et al.Atypical C3 glomerulopathy: conclusions from "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.Kidney Int. 2017; 91: 539-551Abstract Full Text PDF PubMed Scopus (276) Google Scholar,S1–S5 The disease features overactivity alternative...