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Gene control of tyrosine kinase TIE2 and vascular manifestations of infections #MMPMID26884170
Ghosh CC; David S; Zhang R; Berghelli A; Milam K; Higgins SJ; Hunter J; Mukherjee A; Wei Y; Tran M; Suber F; Kobzik L; Kain KC; Lu S; Santel A; Yano K; Guha P; Dumont DJ; Christiani DC; Parikh SM
Proc Natl Acad Sci U S A 2016[Mar]; 113 (9): 2472-7 PMID26884170show ga
Major infections, such as influenza and bacterial sepsis, kill millions of individuals yearly, most commonly from complications affecting the vasculature, such as acute respiratory distress syndrome. Poor outcomes from rare infections, such as Ebola virus disease, have also been linked to the vasculature. The basis for prominent vascular involvement in infectious syndromes remains poorly understood. The present work shows that humans exhibit common, yet highly consequential, genetic variation in the ability to sustain expression of a key homeostatic vascular receptor called tunica interna endothelial cell kinase 2. The results suggest that host determinants of the molecular vascular response to infection may have a heretofore underappreciated impact on clinical outcomes. They also suggest new means to identify at-risk individuals and personalize future therapies.