Background Pregnancy-associated plasma protein-A (PAPP-A) is known to be abundantly expressed in vulnerable plaques in arteriosclerotic disease. Studies have shown PAPP-A to be a sensitive biomarker of plaque instability and cardiovascular events in patients with acute coronary syndrome. This paper tried to determine the association of PAPP-A polymorphisms with acute coronary syndrome (ACS).
Methods A case-control study of 210 patients with ACS and 204 unrelated age and sex matched controls was performed. four single nucleotide polymorphisms (SNPs) of PAPP-A gene variants were detected by PCR-restriction fragment length polymorphism (PCR-RFLP). The serum level of PAPP-A was measured using a newly developed sandwich ELISA technique based on 2 monoclonal antibodies.
Results Mean PAPP-A values were significantly higher in patients with acute coronary syndrome than in those with stable angina pectoris (29.7 vs 15.8 mIU/l, p <0.01). In samples drawn <2 h after admission, the sensitivity of PAPP-A was superior (93%) to that of CK-MB (60%) and troponin T (61%). In the patients with high-risk unstable angina pectoris, PAPP-A was related to the risk of nonfatal myocardial infarction (p=0.02) but not death (p=0.08). This result was consistent on multivariate analysis of the combination of mortality or nonfatal myocardial infarction (OR 2.65, 95% CI 1.40 to 5.03). In patients with non-ST-elevation acute coronary syndrome and ST elevation myocardial infarctions, PAPP-A was related to the risk of death (p=0.01). This was also true after adjustment for other univariate predictors of death (OR 2.19, 95% CI 1.16 to 4.16). Multiple logistic regression analysis with risk factors such as age, male sex, smoking, hypertension, diabetes mellitus, and dyslipidemia revealed the PAPP-A IVS6+95 C allele (dbSNP: rs13290387) to be associated with an increased risk of ACS (OR, 2.44; 95% CI 1.21 to 3.98; p=0.018). The IVS6+95 (G/C) polymorphism in the PAPP-A gene has been reported 102 cases (48.6%) were GG and 80 cases (38.1%) were GC and 28 cases (13.3%) were CC for the ACS group; the respective figures were 116 (56.9%) and 70 (34.3%) and 18 (8.8%) in the controls. Patients carrying the C allele had a tendency to increased risk of ACS.
Conclusions In the early stages of non-ST-elevation acute coronary syndrome and ST elevation myocardial infarctions, PAPP-A seems to be a more sensitive marker of myocardial infarction than CK-MB and troponin T. PAPP-A seems to be valuable in predicting the outcomes of patients admitted with high-risk NSTE-ACS or STEMI. PAPP-A IVS6+95 C allele is an independent risk factor for ACS even after adjustment for traditional risk factors.