ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS.
The intrapulmonary renin-angiotensin system via tissue concentration of angiotensin II or bradykinin may have multiple effects on pulmonary pathophysiology. Therefore, it was investigated whether the presence of the D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism or the A allele of angiotensinogen (AGT) promoter polymorphism (-6)A/G are independent risk factors for 30-day survival in acute respiratory distress syndrome (ARDS) patients. In a prospective study, adults (Germans of Caucasian ethnicity) with ARDS (n = 84) were recruited from the current authors' intensive care unit and genotyped for the ACE I/D and the AGT (-6)A/G polymorphisms, as were 200 healthy Caucasian controls. Mortality was increased in the ACE DD genotype compared with the I allele, and the ACE I/D polymorphism was an independent prognostic factor for 30-day survival. Patients with a homozygous DD genotype were at highest risk for death (hazard ratio 5.7; 95% confidence interval 1.7-19.2) compared with the II genotype. In contrast, the AGT (-6)A/G polymorphism was neither associated with an increased risk for development of ARDS nor with outcome. In patients with acute respiratory distress syndrome, the angiotensin-converting enzyme insertion/deletion polymorphism but not the angiotensinogen (-6)A/G promoter polymorphism is an independent risk factor with a pronounced effect on 30-day survival.
Adamzik
M
M
Institut für Pharmakogenetik, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, Germany. michael.adamzik@uni-essen.de
Frey
U
U
Sixt
S
S
Knemeyer
L
L
Beiderlinden
M
M
Peters
J
J
Siffert
W
W
D000328:Adult; D000483:Alleles; D000809:Angiotensins / Q000235:genetics*; D002872:Chromosome Deletion; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000401:mortality; D012307:Risk Factors; D015996:Survival Rate
D000809:Angiotensins; D007703:Peptidyl-Dipeptidase A