Effect of alpha-2 plasmin inhibitor p.Arg6Trp polymorphism and antigen level on the risk of myocardial infarction in young patients
E. Katona, A. Orosz, Z. Mezei, L. Balogh, Z. Bereczky, I. Edes, L. Muszbek (Debrecen, Hungary)
Time: 17:15 - 18:15
Objective: Alpha2-plasmin inhibitor (a2-PI) is the main physiological inhibitor of plasmin. Increased a2-PI levels have been associated with increased thrombotic risk. Alpha2-PI is a heterogeneous protein, as in the plasma it undergoes both N- and C-terminal cleavages, which significantly modify its activities. In about 70% of circulating a2-PI the N-terminal cleavage by APCE (antiplasmin cleaving enzyme) results in a 12 amino acid residue shorter isoform. This isoform is cross-linked more effectively to fibrin alpha-chain by activated factor XIII; thereby the alteration of the ratio of N-terminal isoforms may influence the fibrinolytic resistance of fibrin clot. The p.Arg6Trp polymorphism of a2-PI may modify the ratio of N-terminal isoforms as APCE cleaves the Arg6 form 8-fold faster than the Trp6 form. In this case-control study the effect of a2-PI p.Arg6Trp polymorphism and a2-PI antigen concentration on the risk of myocardial infarction (MI) in young patients were investigated.
Methods: 109 patients who had coronary sclerosis proven by coronary angiography and suffered MI (MI+) below the age of 40 and two age-matched control groups (n=98 clinical controls without significant coronary stenosis and MI (MI-), and n=139 healthy controls (HC)) were enrolled in the study. Total a2-PI antigen levels were determined by a sandwich type ELISA method, a2-PI Arg6Trp genotype was determined by RT-PCR using LightCycler® 480.
Results: Trp allele frequency did not differ significantly among the study groups and were in good agreement with data obtained from the HapMap database. The presence of Trp allele did not influence the risk for MI when patient groups were compared to the MI- or HC groups. Adjusted total a2-PI antigen levels (mean (95%CI)) were significantly elevated in MI+ patients compared to both controls (MI+: 75.4 mg/L (73.6-77.1), MI-: 72.5 mg/L (70.6-74.3), and HC, 64.0 mg/L (62.5-65.5). Elevated a2-PI level (above 73.3 mg/L) increased the risk of MI (OR MI+ vs HC, 7.25, 95%CI, 3.53-14,87).
Conclusion: In our study, the a2-PI p.Arg6Trp polymorphism had no effect on the risk of MI in young patients, however a2-PI levels in the upper third resulted in a significant risk enhancement.