Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients

Geneviève Galarneau, Sean Coady, Melanie E. Garrett, Neal Jeffries, Mona Puggal, Dina Paltoo, Karen Soldano, Antonio Guasch, Allison E. Ashley-Koch, Marilyn J. Telen, Abdullah Kutlar, Guillaume Lettre, George J. Papanicolaou

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Patients with sickle cell disease (SCD) present with a wide range of clinical complications. Understanding this clinical heterogeneity offers the prospects to tailor the right treatments to the right patients and also guide the development of novel therapies. Several environmental (eg, nutrition) and nonenvironmental (eg, fetal hemoglobin levels, a-thalassemia status) factors are known to modify SCD severity. To find new genetic modifiers of SCD severity, we performed a gene-centric association study in 1514 African American participants from the Cooperative Study of Sickle Cell Disease (CSSCD) for acute chest syndrome (ACS) and painful crisis. From the initial results, we selected 36 single nucleotide polymorphism (SNPs) and genotyped them for replication in 387 independent patients from the CSSCD, 318 SCD patients recruited at Georgia Health Sciences University, and 449 patients from the Duke SCD cohort. In the combined analysis, an association between ACS and rs6141803 reached array-wide significance (P = 4.1 3 10-7). This SNP is located 8.2 kilobases upstream of COMMD7, a gene highly expressed in the lung that interacts with nuclear factor-kB signaling. Our results provide new leads to gaining a better understanding of clinical variability in SCD, a "simple" monogenic disease. (Blood. 2013;122(3):434-442)

Original languageEnglish (US)
Pages (from-to)434-442
Number of pages9
Issue number3
StatePublished - Jul 18 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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