Estudo de polimorfismos nos genes que codificam a aldosterona sintase e o angiotensinogênio e relações de ancestralidade de pacientes com insuficiência cardíaca de etiologia isquêmica e não isquêmica

Abstract

Heart failure (HF) is a clinical and multifactorial syndrome characterized by the inability of the heart to pump blood and meet metabolic tissue needs. Despite therapeutic advances, HF remains one of the main causes of mortality, hospitalization and functional limitations in the country and in the world. The renin-angiotensin-aldosterone system is a possible target for better understanding the mechanisms involved in HF development and its multiple clinical outcomes. The present study aimed to investigate the distribution of allelic and genotypic frequencies of polymorphisms related to aldosterone (CYP11B2 gene) - rs3802228 A>G, rs3097 C>T - and angiotensinogen (AGT gene) production - rs699 A>G e rs3789678 C>T- in a cohort of patients with HF and individuals without the history of the disease and investigate its association with the presence of HF. Genomic Ancestry were also determined to exclude spurious associations. The study included 247 individuals of both sexes attended at the HF outpatient clinic, of which 117 with ischemic HF (I-HF) and 130 with non-ischemic HF (NI-HF). In addition, 122 samples from healthy volunteers were genotyped. DNA samples were extracted by salting-out technique and genotyped by PCR and SnapShot Multipex systems. The mean age of patients was 64,8 ± 13,8 years and healthy subjects 39.9 ± 11.6. The T allele of the rs3097 polymorphism demonstrated a significant association with both ischaemic and non-ischaemic HF in individuals of European (I-HF=0.02, NI-HF=4x10-4) and with ischaemic HF in individuals of admixed (p=8x10-4) ancestry. This work contributed to the characterization of the rs3097, rs3802228, rs699 and rs3789678 polymorphisms in the Brazilian population, more specifically in Rio de Janeiro, and to the association of these polymorphisms with HF, with the help of ancestral molecular tools to eliminate associations spurious. The results showed suggestive associations of the rs3097 C>T polymorphism, present in the aldosterone synthase gene, with both ischaemic and non-ischaemic HF