Association of angiotensin II type 1 receptor-associated protein gene polymorphism with increased mortality in septic shock

Critical Care Medicine
Taka-aki NakadaKeith R Walley

Abstract

Angiotensin II and its postreceptor signaling are crucial in regulating vasomotor tone. The objective of this study was to test the hypothesis that single nucleotide polymorphisms in angiotensin II pathway genes alter outcome of septic shock. Genetic association study and in vitro experiment. Intensive care units at academic teaching centers. Derivation and validation septic shock cohorts (n = 589 and n = 616, respectively) and a coronary artery bypass surgery cohort (n = 551). Patients with septic shock in the derivation cohort were genotyped for tag single nucleotide polymorphisms: angiotensin-converting enzyme (six single nucleotide polymorphisms), angiotensin II receptor type 1 (five single nucleotide polymorphisms), and angiotensin II type 1 receptor-associated protein (three single nucleotide polymorphisms), which is a negative regulator of angiotensin II receptor type 1. Patients in the septic shock replication cohort and the coronary artery bypass graft cohort were genotyped for the angiotensin II type 1 receptor-associated protein rs11121816. The primary outcome variable was 28-day mortality. Secondary outcome variables were blood pressure and heart rate. Angiotensin II type 1 receptor-associated protein messenger RNA ...Continue Reading

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