Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease

James G. Taylor VI, Diana Ackah, Crystal Cobb, Nick Orr, Melanie J. Percy, Vandana Sachdev, Roberto Machado, Oswaldo Castro, Gregory J. Kato, Stephen J. Chanock, Mark T. Gladwin

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Pulmonary hypertension is a common complication of sickle cell disease (SCD) and a risk factor for early death. Hemolysis may participate in its pathogenesis by limiting nitric oxide (NO) bioavailability and producing vasculopathy. We hypothesized that hemoglobin mutations that diminish hemolysis in SCD would influence pulmonary hypertension susceptibility. Surprisingly, coincident α-thalassemia (Odds Ratio [OR] = 0.95, 95% CI = 0.46-1.94, P = NS) was not associated with pulmonary hypertension susceptibility in homozygous SCD. However, pulmonary hypertension cases were less likely to have hemoglobin SC (OR = 0.18, 95% confidence interval [CI] = 0.06-0.51, P = 0.0005) or Sβ+ thalassemia (OR = 0.25, 95% CI = 0.06-1.16, P = 0.10). These compound heterozygotes may be protected from pulmonary hypertension because of reduced levels of intravascular hemolysis, but develop this complication at a lower rate possibly due to the presence of non-hemolytic risk factors such as renal dysfunction, iron overload and advancing age. Despite this protective association, patients with SC who did develop pulmonary hypertension remained at significant risk for death during 49 months of follow-up (Hazard Ratio = 8.20, P = 0.0057).

Original languageEnglish (US)
Pages (from-to)6-14
Number of pages9
JournalAmerican Journal of Hematology
Volume83
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Sickle Cell Anemia
Pulmonary Hypertension
Hemoglobins
Mutation
Hemolysis
Genes
Thalassemia
Odds Ratio
Confidence Intervals
Iron Overload
Heterozygote
Biological Availability
Nitric Oxide
Kidney

ASJC Scopus subject areas

  • Hematology

Cite this

Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease. / Taylor VI, James G.; Ackah, Diana; Cobb, Crystal; Orr, Nick; Percy, Melanie J.; Sachdev, Vandana; Machado, Roberto; Castro, Oswaldo; Kato, Gregory J.; Chanock, Stephen J.; Gladwin, Mark T.

In: American Journal of Hematology, Vol. 83, No. 1, 01.01.2008, p. 6-14.

Research output: Contribution to journalArticle

Taylor VI, JG, Ackah, D, Cobb, C, Orr, N, Percy, MJ, Sachdev, V, Machado, R, Castro, O, Kato, GJ, Chanock, SJ & Gladwin, MT 2008, 'Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease', American Journal of Hematology, vol. 83, no. 1, pp. 6-14. https://doi.org/10.1002/ajh.21035
Taylor VI, James G. ; Ackah, Diana ; Cobb, Crystal ; Orr, Nick ; Percy, Melanie J. ; Sachdev, Vandana ; Machado, Roberto ; Castro, Oswaldo ; Kato, Gregory J. ; Chanock, Stephen J. ; Gladwin, Mark T. / Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease. In: American Journal of Hematology. 2008 ; Vol. 83, No. 1. pp. 6-14.
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