Document Type

Article

Publication Date

4-25-2017

Abstract

a-Thalassemia and the BCL11A rs1427407 T allele are commonly observed in sickle cell anemia (SCA) patients and are associated with reduced hemolysis and higher hemoglobin F levels, respectively. We investigated whether a high-risk genetic profile, defined as SCA patients who did not inherit either a-thalassemia or the BCL11A rs1427407 T allele, had stronger associations with clinical and laboratory variables than the individual genetic components in the University of Ibadan cohort (N 5 249). We then replicated our findings in SCA cohorts from the University of Illinois at Chicago (UIC) (N 5 260) and the Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy study (Walk-PHaSST) (N 5 387). A high-risk genetic profile was associated with higher reticulocytes (15.0% vs 7.8%, P 5 .08) and stroke history (6% vs 1%, P 5 .02) than standard-risk patients, and these associations were more significant than the individual genetic components in the University of Ibadan cohort. These findings were replicated in high-risk patients from UIC and Walk-PHaSST for reticulocytes (UIC: 13.5% vs 11.8%, P 5 .03; Walk-PHaSST: 9.6% vs 8.2%, P 5 .0003) and stroke history (UIC: 32% vs 22%, P 5 .07; Walk-PHaSST: 14% vs 7%, P 5 .01). On combined analysis, a high-risk genetic profile had strong associations with increased markers of hemolysis (hemoglobin b 5 –0.29, 95% confidence interval [CI]: 20.50 to 20.09; P5.006; reticulocyte% b 5 2.29, 95% CI: 1.31-3.25; P 5 1 3 1025) and stroke history (odds ratio 5 2.0, 95% CI: 1.3-3.0; P 5 .0002), but no association with frequent vaso-occlusive crises ($3 per year). A high-risk genetic profile is associated with increased hemolysis and stroke history in 3 independent cohorts. This profile may help identify patients to prioritize for hydroxyurea and for closer monitoring strategies for stroke.

Publication Source (Journal or Book title)

Blood Advances

First Page

693

Last Page

698

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