NOS3, ET1, TGF-β1, and THBS1 polymorphisms modulating clinical complications in sickle cell disease patients

Abstract

Clinical manifestations are highly variable in sickle cell disease (SCD) and polymorphisms (SNP) may modify vascular homeostasis. Because of this, we investigated of SNP of NOS3, ET1, TGF-β1 and THBS1 genes in vascular complications of SCD. High risk of hospitalization was found for genotypes NOS3TC/CC (rs2070744 - RR: 1.94) and THBS1AG/GG (rs1478604 - RR: 1.59) while low risk to NOS3GT/TT (rs1799983 - RR: 0.53). Hydroxyurea treatment was more frequent in the genotypes NOS3TC/CC (rs2070744 - RR: 1.83), ET1GT/TT (rs5370 - RR: 2.67) and ET1TG/GG (rs1800541 - RR: 1.43). Alleles ET1TG/GG (rs1800541) showed correlation for abdominal, arm and leg pain, bone disorders, cholelithiasis and vaso-occlusive crisis, while ET1GT/TT (rs5370) with chest pain, painful episodes, splenic sequestration and stroke. Interestingly, the NOS3GT/TT (rs1799983) alleles had a high stroke risk (RR:4.21), though, protection against bone disorders, cholelithiasis and less risk of hospitalization. We believed that our results indicate polymorphisms that may provide benefits in the treating Clinical Complications in SCD Patients, especially in vascular SCD pathophysiology, modulating vaso-occlusion crisis.