Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease

Allison E. Ashley-Koch, Laine Elliott, Melanie E. Kail, Laura M. De Castro, Jude Jonassaint, Terry L. Jackson, Jennifer Price, Kenneth I. Ataga, Marc C. Levesque, J. Brice Weinberg, Eugene P. Orringer, Ann Collins, Jeffery M. Vance, Marilyn J. Telen

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who had been screened for pHTN by echocardiography (n = 111). Evidence of association was primarily identified for genes in the TGFβ superfamily, including activin A re-ceptor, type ll - Iike 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGFβ pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the (β-1 adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6, and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets, and reducing the occurrence of this life-threatening SCD complication

Original languageEnglish (US)
Pages (from-to)5721-5726
Number of pages6
Issue number12
StatePublished - Jun 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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