El gen anril com a marcador d'episodis cardiovasculars en pacients amb malaltia renal crònica

• Autores: Ariadna Arbiol Roca
• Directores de la Tesis: Nuria Lloberas Blanch (dir. tes.), Ariadna Padró Miquel (dir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2018
• Idioma: español
• Tribunal Calificador de la Tesis: Xavier Pintó Sala (presid.), José Manuel Valdivieso Revilla (secret.), Anna Messeguer Navarro (voc.)
• Programa de doctorado: Programa de Doctorado en Bioquímica, Biología Molecular y Biomedicina por la Universidad Autónoma de Barcelona
• Materias:
  • Química
    • Bioquímica
      • Biología molecular
  • Ciencias médicas
    • Medicina interna
      • Nefrología
• Enlaces
  • Tesis en acceso abierto en:  TESEO  TDX 
• Resumen

  • ABSTRACT The main objective of this doctoral thesis was to ascertain whether ANRIL and CARD8 single nucleotide polymorphisms (SNPs) could identify risk of major adverse cardiovascular event (MACE) in chronic renal disease: hemodialysis and kidney transplant recipients.

    The thesis was divided into two parts: in the first part, the objective was to ascertain whether ANRIL polymorphisms could identify risk of major adverse cardiovascular event in patients starting on hemodialysis. And, in the second part, the main objective was to ascertain whether the statistically significant polymorphism of the first study continues to play its role in promoting cardiovascular events once the patients have undergone renal transplantation.

    This thesis shows a correlation between ANRIL SNP rs10757278 and MACE in hemodialysis patients. Specifically, homozygous patients for the risk allele (GG genotype) showed 2.15 (1.14-4.01), Paj=0.018 fold higher risk of MACE during hemodialysis than carriers of the protective allele (AA or AG). Furthermore, this effect was maintained despite adjusting for the classic cardiovascular risk variables, including diabetes, with which it maintains a synergistic effect.

    This relationship between ANRIL polymorphism and major adverse cardiovascular events was confirmed in the second study in renal transplant recipients cohort. Patients homozygous for the risk allele (GG genotype) showed a 2.93 (1.69–5.11), P<0.0001 fold higher risk of suffering a cardiovascular event than patients carrying the protective allele (AA or AG genotype). A stratified analysis by type of cardiovascular event: ischemic stroke or myocardial event (myocardial infarction and unstable angina) was performed. ANRIL polymorphism rs10757278 showed a stronger association with ischemic stroke HR = 4.43 (1.81–10.85), Paj=0.001 than with myocardial event (HR = 2.27 (1.10–4.67), Paj=0.026.

    Regarding CARD8 polymorphism, no association was observed between CARD8 SNP rs2043211 and cardiovascular events nor all cause mortality nor cardiovascular exitus in renal transplant recipients. However, the effect of the ANRIL SNP rs10757278 was maintained when it was analyzed in combination with CARD8, suggesting that CARD8 SNP rs2043211 could play a role in the ANRIL SNP rs10757278 mechanism.

    Results obtained in this doctoral thesis demonstrate, for the first time, a significant genotypic association of ANRIL SNP rs10757278 with major adverse cardiovascular events, in particular with ischemic stroke, in chronic kidney disease patients. The study of this polymorphism would be beneficial for the management of high cardiovascular risk patients resulting in a personalized treatment that could reduce the morbidity and mortality.