The Relationship Between The Levels Of Circulating Endothelial Progenitor Cells And Aldehyde Dehydrogenase-2 Polymorphisms In Patients With Acute Myocardial Infarction

Objectives1. To study the relationship between the levels of circulating endothelial progenitor cells(EPCs) CD34~+KDR~+ and Aldehyde dehydrogenase-2(ALDH2) polymorphisms in patients with acute myocardial infarction.2. To evaluate the role that serum high sensitive C reactive protein(hs-CRP) plays in the relationship.MethodsA case-control study method was adopted. 101 in-hospital patients with acute myocardial infarction (AMI) and 30 healthy people coming for physical examination, who came to Qilu Hospital of Shandong University from March 2007 to January 2008, were enrolled in this study. The basic data were collected using a structured questionnaire containing the subjects' clinical characteristics, including age, gender, smoking, hypertension, diabetes, hypercholesterolemia, family history of coronary heart disease (CHD). In the AMI group, the levels of peripheral circulating EPCs CD34~+KDR~+ were assessed using Fluorescence Activated Cell Sorter (FACS), and the serum hs-CRP contents were measured with immuno-turbidity. At the same time, the genotypes of ALDH2 were determined by polymerase chain reaction and direct sequencing. The relationship between the levels of circulating EPCs and the cardiovascular risk factors as well as ALDH2 gene polymorphisms were analyzed. And the role that serum hs-CRP plays in the relationship between the EPCs and ALDH2 gene polymorphisms was evaluated using a multi-variable liner regression.Results1. In the patients with AMI, smoking, diabetes, mutant ALDH2 genotypes were associated with significantly lower EPCs levels(P<0.05). It was also observed that low density lipoprotein-cholesterol (LDL-C) was negatively correlated with the EPCs levels (R=-0.357, P<0.05).2. The levels of circulating EPCs and serum hs-CRP in AMI group were significantly higher than those in control group(P<0.001), and there was positive correlation between EPCs and hs-CRP levels (R=0.631, P<0.001) . But the distribution of mutant ALDH2 genotypes frequency were similar between the two groups.3. In the AMI group, the levels of circulating EPCs and serum hs-CRP were significantly higher in the patients with mutant ALDH2 genotypes than those in ones with wide genotypes(P<0.001).4. In the AMI group, after adjustment for ALDH2 genotypes, age, gender, smoking, hypertension, diabetes, family history of CHD, LDL-C, HDL-C, TC, TG using a multi-variable liner regression, the mutant ALDH2 genotypes, smoking, LDL-C were risk factors for the EPCs levels, and the Beta values were -0.349,-0.255,-0.218, respectively. However, inclusion of hs-CRP as one of the independent variables downplayed the importance of the mutant ALDH2 genotypes(Beta value was -0.174, P=0.037), and hs-CRP was a protective factor for the EPCs levels (Beta value was 0.329, P=0. 013) . And after adjustment for the above-mentioned independent variables, the mutant ALDH2 genotypes affected the levels of hs-CRP (Beta value was -0.198, P=0. 029).Conclusions1. In the patients with AMI, the levels of peripheral circulating EPCs was inversely associated with the traditional cardiovascular risk factors.2. The levels of circulating EPCs and serum hs-CRP increased obviously in the patients after AMI, and there was positive correlation between them. That is to say, the rising of serum hs-CRP levels may contribute to the mobilization of bone marrow derived-EPCs. 3. In the AMI group, the mutant ALDH2 genotypes was a risk factor for the levels of circulating EPCs and serum hs-CRP. In other words, the increasing of the levels of EPCs and hs-CRP in the patients with mutant genotypes was no so marked as that in ones with wide genotypes once AMI happened, and the serum hs-CRP might affect as an intermediate agent. Therefore, the mutant ALDH2 genotypes may have influence on the prognosis of AMI; namely, it can be a indicator of prognosis for AMI clinically.