Efeito dos polimorfismos nos genes MTHFR (C677T / A1298C / A1625C), MTRR (A66G / C524T) e SERPINE-1 (G43A) na Hiperhomocisteinemia de recém-nascidos com diagnóstico de Cardiopatia Congênita

Abstract

The congenital heart disease (CHD) is a collective of conditions which impact the structure and cardiocirculatory function and can varies it presentation at severity. Despite advances in detection methods, the gold standard is limited to imaging tests and considering the irregular distribution of hospital centers, it is believed that up to 50% of patients remain undiagnosed in Brazil, being the second leading cause of death among newborns lagging behind infectious diseases. There’s a considerable evidence of that genetic factors contribute to several conditions to predispose the development of CHD or associated with their presence. The aim of this study is to investigate the frequency of the polymorphisms MTHFR C677T (rs1801133), A1298C (rs1801131), A1625C (rs145641996), MTRR A66G (rs1801394), C524T (rs1532268) and SERPINE-1 G43A (rs6092) in newborns (NB) carries of the CHD and associate with the total plasma homocysteine level (tHcy), folic acid and cobalamin levels attended of cardiac reference center at Manaus-Amazonas. The study population was composed of 173 puerperal women-newborns pairs (Control Group) and 72 puerperal women-newborn pairs with newborns diagnosed with heart disease (Group Patients), between March 2018 and October, 2019. Were observed a higher frequency of maternal gestational diabetes and prematurity in the case mother group (OR: 6.04; 95% CI: 1.79-20.29; p<0.001) and (OR: 3.20; 95 % CI: 1.76-5.85; p<0.001). Low birth weight among cases NB (2.7±0.73kg) was significant (p<0.001), when compared to control NB (3.47±0.53kg). The allelic frequency of the SNP rs1801133, rs1801394 and rs1532268 were higher on cases NB than controls NB, as the prevalence associated with higher levels of tHcy. The predict range of the Hcy measurement between cases NB expressed a significative area under the ROC curve (AUC=0.939; 95%CI 0.912-0.966 - p<0.001). Gestational Diabetes, Prematurity and low weight income were risk factors to CHD. The levels of tHcy were high in NB, mainly associated to 677TT of MTHFR and 66GG and 524TT of MTRR genotypes, regardless of the presence CHD cases or controls, although much higher in cases. We suggest that serum tHcy levels >15.48μmol/L may be a valuable reference point as a predictor CHD.