Correlation Between MPO Genetic Polymorphism And Coronary Heart Disease And A Preliminary Study Of Its Possible Mechanism

Objective To study the relationship among myeloperoxidase(MPO) genetic polymorphism, plasma MPO levels and coronary heart disease. And by evaluating the relationship between MPO and CD11b/CD18 in polymorphonuclear neutrophils (PMNs) cellular membrane, and the effect of MPO inhibitor on the adhesion of PMN to ECV304 cells, we aims to investigate the preliminary mechanism of MPO..Methods We conducted a case-control study of 235 subjects who all underwent coronary angiography. Subjects (n=157) with≥50% stenosis in at least one coronary vessels were defined as CHD . Subjects (n=78) without any stenosis in all coronary vessels were defined as controls. MPO-463 genotyping was performed using PCR and restriction fragment length polymorphism analysis(RFLP). Total plasma MPO levels were measured by ELISA, hs-CRP by immunoturbidimetry, cTnI levels by immunofluorescence. IMA was assayed by the albumin cobalt binding test. And the expression of CD11b/CD18 on the PMNs was measured by the Flow cytometry (FCM).The capacity of PMNs adhesion to ECV304 cells was evaluated by adhesion assay.Results 1. Mean total plasma MPO level was significantly higher in CHD patients (332.05±167.56pg/ml) than that in controls (277.81±142.68pg/ml) (P<0.05). 2. There were three kinds of genetypes of MPO: GG GA AA. The frequencies of the three genetypes were significantly different between CHD groups and controls (P<0.05). Patients with the GG genotype had an increased risk of CAD(odds ratio 4.070, 95%confidence interval 1.472-11.253,P<0.01). In the two groups, the difference of the MPO levels among the three genetypes is significant (P<0.001). In the CHD group, the MPO levels with GG were significantly higher than that in individuals with GA(P=0.007<0.05) and AA(P=0.002<0.05). However, there was no significantly different of MPO levels between individuals with GA and individuals with AA (P=0.661>0.05). 3. Compared with the control group, the adhesion rate between PMN and ECV304 in AMI group was much higher [(47.63±10.16)%vs(8.82±2.63)%,P<0.01] ,and anti-CD11b antibody , MPO inhibitor ABAH(10μM,20μM) can significantly decrease this effect(P<0.05).Conclusions 1.Plasma MPO level is associated with CHD. 2. Polymorphism of MPO correlates with CHD and it may be a possible genetic factor of CHD. Allele G is associated with the MPO level in CHD group. 3. MPO inhibitor ABAH can decrease the adhesion of PMN to ECV304, and it may be a result of its effect on the expression of CD11b.