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OP0037 Fibrinolytic system and ace i/d polymorphism in systemic sclerosis
  1. C Angotti1,
  2. F Gensini2,
  3. C Fatini2,
  4. B Battaglini3,
  5. E Sticchi3,
  6. S Fedi4,
  7. A Righi1,
  8. G Pepe5,
  9. R Abbate4,
  10. M Matucci Cerinic1
  1. 1Department Internal Medicine, Section of Rheumatology
  2. 2Department Clinical Physiopathology, Sect of Gen
  3. 3Department Medicine and Surgery
  4. 4Thromb Cent, University of Florence, Florence
  5. 5Deptarment Internal Medicine, University Tor Vergata, Rome, Italy


Background In Systemic sclerosis (SSc), an imbalance of the fibrinolytic system was shown. In vivo and in vitro studies suggest a role for Renin Angiotensin System in the regulation of fibrinolytic balance: Angiotensin II (Ang II) increases the plasminogen activator inhibitor?1 (PAI-1) production and secretion, and ACE reduces t-PA production. A polymorphism in the ACE gene consisting of an insertion or deletion (I/D) of 287 bp fragment in intron 16 was described. The D allele of ID polymorphism is associated with an increased level of ACE and ACE gene polymorphism may influence the production of Ang II.

Objectives To investigate possible alterations in the fibrinolytic system and to examine the role of ACE I/D polymorphism in SSc.

Methods PAI-1 activity, t-PA and D-Dimer plasma levels were measured in 61 SSc patients (36 limited, 25 diffuse) and 108 healthy controls. ACE I/D polymorphism was genotyped by PCR. PAI-1 activity and t-PA levels were assayed by chromogenic method and D-Dimer levels by ELISA.

Results A significant difference in ACE genotype distribution (chi2 = 9.79 p = 0.007) and allele frequency was observed between patients and controls (0.64 vs 0.50 p = 0.009). In limited SSc a higher frequency of ACE D allele was found (0.68 vs 0.56 in diffuse SSc p = 0.23). By univariate analysis an association between ACE D allele and limited, but not diffuse SSc, was found (OR DD+ID/II = 6.44 95% CI 1.45–28.54 p = 0.005 and OR DD+ID/II = 1.91 95% CI 0.60–6.08 p = 0.31 respectively). Median values of PAI-1, t-PA and D-Dimer were 6.2 U/ml (range 1–37.5),10.5 ng/mL (range 4.3–28.1) and 156 ng/mL (range 64–1064, respectively. Patients had higher t-PA and D-Dimer mean levels than controls (p = 0.000001 and p = 0.02, respectively). No difference was observed in PAI-1 plasma levels between patients and controls (p = 0.85). No association between high PAI-1, t-PA and D-Dimer plasma levels and ACE D allele was observed.

Conclusion These data suggest that ACE D allele is highly associated with limited SSc. Thus, we could hypothesise that this allele may represent a risk factor for the development of limited SSc. Other mechanisms than the alterations of fibrinolytic system may have a role in determining the microvascular damage.

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