Vnitr Lek 2009, 55(12):1135-1140

Nuclear receptors gene polymorphisms and risk of restenosis and clinical events following coronary stenting

P. Neugebauer^1,*, M. Goldbergová-Pávková², P. Kala¹, O. Boček¹, P. Jeřábek¹, M. Poloczek¹, M. Vytiska¹, J. Pařenica¹, R. Mikulík³, J. Jarkovský⁴, B. Semrád¹, J. Špinar¹, A. Vašků²

¹ Interní kardiologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jindřich Špinar, CSc., FESC

² Ústav patologické fyziologie Lékařské fakulty MU Brno, přednostka prof. MUDr. Anna Vašků, CSc.

³ Neurologická klinika Lékařské fakulty MU a FN sv. Anny Brno, přednosta prof. MUDr. Ivan Rektor, CSc.

⁴ Institut biostatistiky a analýz Lékařské a Přírodovědecké fakulty MU Brno, přednosta doc. RNDr. Ladislav Dušek, Ph.D.

Introduction:
Hereditary factors connected with inflammation and fibroproliferation may play important role in restenotic process after coronary stenting. Peroxisome proliferator-activated receptors (PPAR) and retinoic X receptors (RXR) regulate the transcription of crucial genes involved in the glucose and lipid metabolism, inflammation and cell differentiation.

Methods:
In our angiographic and clinical study we assessed the association of gene polymorphisms of L162V for PPAR-α, C161T for PPAR-γ and A(39526)AA for RXR-α with the risk of restenosis and cardiac events after coronary stenting. Primary endpoint was diameter stenosis ≥ 50% at follow-up angiography. Secondary endpoints were death, myocardial infarction and/or target lesion revascularisation at 12 months, and clinical restenosis. The results were adjusted for known predictors of restenosis. The genotypes were analysed by polymerase chains reaction (PCR) and restriction fragment length polymorphism (RFLP) methods.

Results:
Control angiography was performed in 477 of 565 patients (84.4%) with following restenosis rates in genotype subgroups: CC 29.0% vs GC/GG 22.6% (p = 0.33) in L162V, CC 29.9% vs TC/TT 24.6% (p = 0.24) in C161T and A/A 26.9 % vs A/AA + AA/AA 35.0 % (p = 0.14) in A(39526)AA polymorphisms. The T allele of C161T polymorphism was associated with lower frequency of clinical restenosis (p = 0.015).

Conclusion:
We could not find an association of L162V PPAR-α, C161T PPAR-γ and A(39526)AA RXR-α gene polymorphisms with angiographic in-stent restenosis or major cardiac events. However, we found the relationship between C161T PPAR-γ polymorphism and clinical restenosis deserving further study.

Keywords: in-stent restenosis; gene polymorphism; nuclear receptors

Received: May 26, 2009; Accepted: August 26, 2009; Published: December 1, 2009  Show citation