Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis.
OBJECTIVE
The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis.


METHODS
Patients older than 18 years admitted to the intensive care unit (ICU) with the diagnosis of severe sepsis were prospectively included. A blood sample was drawn on the first day of ICU admission, and DNA was extracted. We genotyped the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene (polymerase chain reaction) and the following single-nucleotide polymorphisms (TaqMan SNP genotyping assay): tumor necrosis factor α -376 G/A, -308 G/A, and -238 G/A; interleukin 8 -251 T/A; pre-B cell colony-enhancing factor -1001 G/T; and vascular endothelial growth factor +405 C/G and +936 C/T. Polymorphisms were selected based on reports on their association with ARDS. Variables associated in univariate analysis (P < 0.1) with the diagnosis of ARDS were included in a multiple logistic regression analysis.


RESULTS
We studied 149 patients, of whom 35 presented ARDS. Variables included in the maximal multivariate model were male sex, chronic alcoholism, use of ACE inhibitors or angiotensin-receptor blockers, Simplified Acute Physiology Score II score, serum glucose concentration at ICU admission, and the presence of the allele D of the ACE gene. After adjustment for those variables, the presence of the allele D of the ACE gene (odds ratio, 4.75; 95% confidence interval, 1.02-22.20; P = 0.048) was significantly associated with the diagnosis of ARDS.


CONCLUSIONS
The presence of the allele D of the ACE gene is associated with ARDS in patients with severe sepsis.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, CIBERES, Madrid, Spain.
Pablo
P
Cardinal-Fernández
Antonio
A
Ferruelo
Mariam
M
El-Assar
Catalina
C
Santiago
Félix
F
Gómez-Gallego
Ana
A
Martín-Pellicer
Fernando
F
Frutos-Vivar
Oscar
O
Peñuelas
Nicolás
N
Nin
Andrés
A
Esteban
José A
JA
Lorente
D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012083:Renin / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D018805:Sepsis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
D012083:Renin