Association of Thrombospondin-1 Gene Polymorphism with Elevated Tricuspid Regurgitant Velocity in Sickle Cell Anemia

Background: Pulmonary hypertension (PH) is associated with premature mortality in adults with sickle cell anemia (SCA). Decreased nitric oxide bioavailability has been implicated in the pathogenesis of SCA associated PH. Thrombospondin-1 (TSP1) protein encoded by THBS1 gene inhibits nitric oxide/cGMP signaling and has been hypothesized to promote PH in SCA (Novelli et al. Am J Physiol Lung Cell Mol Physiol 2019). Recently in a cross-sectional targeted gene analysis in adults with SCA, THBS1 gene single nucleotide polymorphisms (SNPs) rs1478605-G and rs1478604-T were found to be associated with PH, as estimated by its surrogate echocardiogram marker tricuspid regurgitant velocity (TRV). However, neither of these SNPs were validated in an external cohort (Jacob et al. Am J Hematol. 2017).