Angiotensin-converting enzyme polymorphism affects outcome of local Chinese with acute lung injury

Abstract

Introduction: Acute Lung Injury (ALI) with genetic predisposition is fatal. Relationship between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism and the prognosis of local Chinese patients with ALI was investigated; meanwhile, the mechanisms involved were explored.

Methods: 101 ALI patients, 408 non-ALI patients and 236 healthy blood donors were enrolled. ACE I/D polymorphism was detected by polymerase chain reaction, then ACE genotype (II, ID, DD) and allele (I, D) frequencies were compared. Clinical data of ALI patients was calculated. Also, peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers with different ACE genotypes. Lipopolysaccharide (LPS)-induced ACE gene mRNA expression and ACE activity was measured.

Results: There was no significant difference in the frequencies of the genotypes and alleles. Acute Physiology and Chronic Health Evaluation (APACHE) II score was higher in DD subgroup than in II subgroup (19.7 ± 8.7 and 15.6 ± 6.2; P < 0.05). The 28-day mortality was significantly different (17.4%, 26.8%, and 64.3% for II, ID, and DD; P = 0.013). DD genotype was the independent prognostic factor for 28-day outcome. Furthermore, LPS-induced ACE mRNA expression and ACE activity from PBMC in DD genotype subgroup were both significantly higher than those in the other two subgroups.

Conclusions: ACE I/D polymorphism is a prognostic factor for ALI. Patients with the DD genotype have higher mortality of ALI. Polymorphism influences the expression of ACE gene in LPS-stimulated PBMC, DD genotype leads to higher level of mRNA and enzyme activity. It may be one of the mechanisms involved.

Figure 1

Effect of ACE I/D genotype polymorphism on the 28-day survival rate of ALI (Kaplan–Meier method). ^aP<0.05 vs II subgroup and ^bP<0.05 vs ID subgroup.

Figure 2

Effect of ACE I/D genotype polymorphism on ACE mRNA expression (A) and ACE activity (B) of LPS-induced PBMC. PBMC was exposed to LPS (0.1 μg/ml) for 6 h, and then total RNA was isolated and RT-PCR was performed. Also, the cellular supernatant was collected for the following ACE activity determination. Data are the mean ± s.d. of three experiments. ^aP<0.05 vs vehicle control, ^bP<0.05 vs II group.