Genetic Polymorphisms Associated With Susceptibility and Outcome in ARDS

Recent advances in genetic predisposition to clinical acute lung injury

“…With this backdrop, it is reasonable that many of the candidate genes studied to date fall within these specific pathways. Some of the most compelling associations have been between specific gene polymorphisms and susceptibility and/or outcomes of ALI in genes encoding surfactant proteins (SPs) (39,54,64,77); angiotensin converting enzyme (ACE) (2,48,60); proinflammatory cytokines [TNFA/TNFB (40), IL6 (31,61,73,87), IL8 (44), PBEF1 (10,97), MIF (32), and VEGF (66, 99)] and anti-inflammatory cytokine IL10 (38,83). The most replicated genes include IL6, SFTPB, and ACE.…”

TRALI – Definition, mechanisms, incidence and clinical relevance

“…For example, polymorphisms in the SP-B gene have been associated with the development of ALI (44)(45)(46)(47). Homozygosity for the deletion polymorphism in the angiotensin converting enzyme (ACE) gene which is associated with higher ACE levels and activity was found in an increased frequency among patients with ALI (47).…”

Genetic disruption of the Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling

“…GSH, acting by protein glutathionylation, is being recognized as a potential modulator of the activities of the redox-sensitive thiol proteins, especially those that are involved in signal transduction, and are known to regulate cell growth, differentiation and cell-cycle progression (Fratelli et al, 2004Ghezzi et al, 2005;Shelton et al, 2005;Dalle-Donne et al, 2007b;Gallogly and Mieyal, 2007) Marshall et al, 2002), MEKK1 (Cross and Templeton, 2004), tyrosine phosphatases (Townsend et al, 2006), p53, NF-kB, c-Jun and c-Fos (Klatt and Lamas, 2002;Reynaert et al, 2006;Velu et al, 2007). Thus, it is likely that diminished levels of GSH in Nrf2 À/À cells and GSHdepleted Nrf2 þ / þ cells may cause dysregulation of other signal transduction pathways and the effector transcription factor activation required for gene expression.…”