A striking finding of recent genome wide association studies (GWAS) is the consistent and diverse genome- wide significant associations of the ABO glycotransferase locus with heart and blood phenotypes. These include acute myocardial infarction (AMI), coronary artery disease, venous thrombo-embolism, as well as multiple cardiopulmonary biomarkers traits such as circulating levels of VonWillebrand factor (VWF), Factor VIII, soluble ICAM-1, soluble E-selectin, and LDL cholesterol. We have extended these findings to show nominal associations of the ABO locus with acute lung injury (ALI) and complications of obstructive sleep apnea. These data indicate an important mechanistic role for ABO glycotransferase activity and cell-specific and circulating ABO glycoprotein modifications in cardiopulmonary diseases while also underscoring an underappreciated role for complex carbohydrate modifications in diverse heart, lung, blood and sleep (HLBS) disorders. Using unbiased mass-spectrometry approaches, we propose to define, disease (AMI and ALI) and cell (platelets and endothelium) specific ABO glycoproteomes in order to develop glycopeptide markers of HLBS disease risk and cross-organ, mechanism-based phenotypes in HLBS.
(See Instructions): Recent genomic studies reveal diverse associations of the ABO locus, encoding a glycotransferase, with heart and blood phenotypes. These include myocardial infarction, coronary artery disease and multiple cardiopulmonary biomarkers traits. We propose to define disease and cell-specific ABO glycoproteins in order to develop glycoproteomic classification and prediction across several cardiopulmonary disease traits.
|Manichaikul, Ani; Wang, Xin-Qun; Zhao, Wei et al. (2016) Genetic association of long-chain acyl-CoA synthetase 1 variants with fasting glucose, diabetes, and subclinical atherosclerosis. J Lipid Res 57:433-42|
|Ferguson, Jane F; Xue, Chenyi; Hu, Yu et al. (2016) Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans. J Nutr Biochem 30:126-32|
|Shah, Rachana; Matthews, Gregory J; Shah, Rhia Y et al. (2015) Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 66:266-73|
|Patel, Parth N; Shah, Rhia Y; Ferguson, Jane F et al. (2015) Human experimental endotoxemia in modeling the pathophysiology, genomics, and therapeutics of innate immunity in complex cardiometabolic diseases. Arterioscler Thromb Vasc Biol 35:525-34|
|Zhong, Ming; Zhang, Hanrui; Reilly, John P et al. (2015) ABO Blood Group as a Model for Platelet Glycan Modification in Arterial Thrombosis. Arterioscler Thromb Vasc Biol 35:1570-8|
|Reilly, John P; Anderson, Brian J; Mangalmurti, Nilam S et al. (2015) The ABO Histo-Blood Group and AKI in Critically Ill Patients with Trauma or Sepsis. Clin J Am Soc Nephrol 10:1911-20|
|Bauer, Robert C; Tohyama, Junichiro; Cui, Jian et al. (2015) Knockout of Adamts7, a novel coronary artery disease locus in humans, reduces atherosclerosis in mice. Circulation 131:1202-13|
|Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V et al. (2015) Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics. Arterioscler Thromb Vasc Biol 35:1880-8|
|Ferguson, Jane F; Shah, Rhia Y; Shah, Rachana et al. (2015) Activation of innate immunity modulates insulin sensitivity, glucose effectiveness and pancreatic Î²-cell function in both African ancestry and European ancestry healthy humans. Metabolism 64:513-20|
|Zhang, Hanrui; Xue, Chenyi; Shah, Rhia et al. (2015) Functional analysis and transcriptomic profiling of iPSC-derived macrophages and their application in modeling Mendelian disease. Circ Res 117:17-28|
Showing the most recent 10 out of 30 publications