ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS
ABSTRACT 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.
[Show abstract] [Hide abstract]
ABSTRACT: Angiotensin-converting enzyme (ACE) is the core enzyme in the renin-angiotensin system (RAS), which catalyzes the production of angiotensin II (Ang II). The aim of this study was to determine whether ACE gene is associated with the development of the periodontal disease. To investigate whether ACE is involved in the development of the periodontal disease, 199 periodontal disease patients and 165 control subjects were studied. The ACE insertion/deletion polymorphism was analyzed using polymerase chain reaction (PCR). SNPStats and SPSS 18.0 were used for the analysis of genetic data. Logistic regression models were performed to determine odds ratio (OR), 95% confidence interval (CI), and P value. Genotypic frequencies of I/I, I/D, and D/D were 25.4%, 42.3%, and 32.3% vs. 35.3%, 41.7%, and 23.1% (periodontal disease group vs. control group), respectively. In the genotype analysis of the ACE insertion/deletion polymorphism, codominant and log-additive models both showed significant association with periodontal disease [OR=1.94, 95% CI=1.05-3.61, P=0.036 in the codominant model (I/I vs. D/D); OR=1.39, 95% CI=1.02-1.90, P=0.034 in the log-additive model (I/I vs. I/D vs. D/D)]. These results suggest that the ACE insertion/deletion polymorphism may be associated with the susceptibility to the periodontal disease in the Korean population. Copyright © 2014 Elsevier Ltd. All rights reserved.Archives of Oral Biology 12/2014; 60(3):496-500. DOI:10.1016/j.archoralbio.2014.12.003 · 1.88 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Background Apolipoprotein A1 (ApoA1) is the major apoprotein constituent of high density lipoprotein (HDL) which exerts innate protective effects in systemic inflammation. However, its role in the acute lung injury (ALI) has not been well studied. In the present study we investigated the association between polymorphisms of ApoA1 gene and ALI in a Chinese population. Methods Three polymorphisms of the ApoA1 gene (rs11216153, rs2070665, and rs632153) were genotyped by TaqMan method in 290 patients with sepsis-associated ALI, 285 patients sepsis alone and 330 age- and sex-matched healthy controls. Results We found rs11216153 polymorphism of ApoA1 was associated with ALI, the GG genotype and G allele was common in the ALI patients (76.9%, 88.1%, respectively) than both in the control subjects (55.8%, 75.8%, respectively) and in the sepsis alone patients (58.2%, 78.4%, respectively). Haplotype consisting of these three SNPs strengthened the association with ALI susceptibility. The frequency of haplotype GTG in the ALI samples was significantly higher than that in the healthy control group (OR = 2.261, 95% CI: 1.735 ~ 2.946, P <0.001) and the sepsis alone group (OR = 1.789, 95% CI: 1.373 ~ 2.331.P < 0.001). Carriers of the haplotype TTG had a lower risk for ALI compared with healthy control group (OR = 0.422, 95% CI: 0.310 ~ 0.574, P < 0.001) and sepsis alone group (OR = 0.491, 95% CI: 0.356 ~ 0.676, P <0.001). Conclusions These results indicated that genetic variants in the ApoA1 gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population.Lipids in Health and Disease 05/2014; 13(1):79. DOI:10.1186/1476-511X-13-79 · 2.31 Impact Factor
Article: Future therapies for ARDS[Show abstract] [Hide abstract]
ABSTRACT: IntroductionDespite more than 150 randomized clinical trials (RCTs) of multiple potential therapies, the only interventions for acute respiratory distress syndrome (ARDS) that reduce mortality are those that minimize ventilator-induced lung injury . This ‘translational failure’ may have a number of explanations. Firstly, ARDS is a syndrome, and interventional trials in ARDS generally include a heterogenous patient group with a wide spectrum of disease etiology and disease severity. Second, deficits exist in our understanding of key aspects of the pathogenesis of ARDS. Notwithstanding these challenges, a number of promising therapies are currently under investigation for ARDS, and offer hope for the future.Future therapies for ARDSAspirinPlatelets are important in ARDS pathogenesis. In pre-clinical studies, aspirin reduces thromboxane A2, P-selectin, and platelet-derived chemokine (e.g., CCL5 and CXCL4) production, reduces platelet–neutrophil aggregates and neutrophil extracellular t ...Intensive Care Medicine 12/2014; 41(2). DOI:10.1007/s00134-014-3578-z · 5.54 Impact Factor