Susceptibility to vascular complications in sickle cell anemia patients is associated with intron 4a/b polymorphism of the NOS3 gene: A meta-analysis

Abstract

BackgroundSickle cell anemia (SCA) is characterized by chronic hemolysis and vaso-occlusive episodes. The endothelial dysfunction in SCA may be due to the deficiency of nitric oxide. The association between nitric oxide synthase (NOS3) gene polymorphisms (−786 T > C, 894G > T and intron 4a/b) and risk of vascular complications remains elusive. ObjectiveHere we performed a meta-analysis to evaluate the relationship between NOS3 gene polymorphisms and vascular complications of SCA. MethodsTen previously published articles were retrieved from PubMed, and Embase bibliographic databases. This meta-analysis included, eight papers (463 SCA patients with complications and 333 without complications) that pertained to the NOS3 -786 T > C, five papers (235 SCA patients with complications and 191 without complications) that corresponded to the NOS3 894G > T polymorphism and six papers (391 SCA patients with complications and 292 without complications) that involved the NOS3 intron 4a/b polymorphism. Pooled analysis, sensitivity analysis and assessment of publication bias were performed. ResultsResults of pooled analysis revealed that the NOS3 intron 4a/b polymorphism was significantly associated with an increased risk of vascular complications (aa+ab Vs. bb: odds ratio = 3.28, 95% confidence interval = 1.19–9.02, p = 0.022, random-effect model). However, no significant association was found for NOS3 -786 T > C and 894G > T polymorphisms. ConclusionDespite some limitations, our meta-analysis suggests that NOS3 intron 4a/b polymorphism is associated with four fold-increased risk of vascular complications in sickle cell anemia.