The Differential Expression of Circulating MicroRNAs in Sickle Cell Trait and Sickle Cell Anemia compared to the Normal Hemoglobin Phenotype.

The heterozygous inheritance of the sickle cell gene, called sickle cell trait (HbAS), was previously thought to be benign. HbAS is now associated with an increased risk for chronic kidney disease, pulmonary embolisms, and exertional rhabdomyolysis. The role of gene expression, as regulated by microRNAs, in these clinical HbAS associations has not been investigated. We explored the association between HbAS and the differential expression of circultaing (plasma) microRNAs when compared to the normal hemoglobin phenotype (HbAA). In stark contrast, the homozygous inheritance of the sickle cell gene, called sickle cell anemia (HbSS) is a severe disease that was previously associated with early mortality and severe morbidity. With appropriate care and early interventions, people with HbSS have improved life expectancy but still experience significant morbidity including cardiac, kidney, and pulmonary disease. The role of gene expression as regulated by microRNA in these clinical HbSS associations has not been investigated. We also explored whether the presence of HbSS is associated with the differential expression of circultaing (plasma) microRNAs as compared to the normal hemoglobin phenotype (HbAA). Circulating microRNA profiles in frozen plasma samples obtained from self-identified Black race human subjects with HbAS, HbSS, and HbAA selected from the Mass General Brigham Biobank. HbAA (controls) were matched to HbAS (1:1) and HbSS (1:3) based on age, sex, and eGFR. All subjects were healthy with no comorbidities.