Endothelial nitric oxide synthase gene polymorphisms and the risk of vasculopathy in sickle cell disease

Sickle cell disease (SCD) is one of the major health problems in many parts of the world. SCD is characterized by multisystem complications with marked variability in its severity between patients, probably linked to nitric oxide (NO). Endothelial nitric oxide synthase (eNOS) enzyme which is responsible for NO synthesis may be implicated in SCD pathophysiology.

To explore the possible association between the eNOS gene polymorphisms and severity of SCD. Furthermore, we examined the genomic diversity of these polymorphisms in SCD patients.

We genotyped 100 SCD patients and 80 controls were genotyped for eNOS 4a/b and eNOS 786T>C polymorphisms, using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism assay, respectively. Polymorphisms were analyzed in relation to severity of SCD manifestations.

The homozygous mutant eNOS-786T>T genotype was significantly associated with high risk of acute chest syndrome (ACS). The wild-type eNOS-4a/4b genotype was protective against vaso-occlusive crisis (VOC) and pulmonary hypertension (PHTN). The mutant homozygous haplotype (C -4a) was significantly associated with the risk of ACS, VOC, and PHTN.

eNOS intron 4 and eNOS T>C gene polymorphisms may be used as a genetic marker of prognostic value in SCD, as they are associated with unfavorable clinical outcomes.