TY - JOUR
T1 - Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients
AU - Galarneau, Geneviève
AU - Coady, Sean
AU - Garrett, Melanie E.
AU - Jeffries, Neal
AU - Puggal, Mona
AU - Paltoo, Dina
AU - Soldano, Karen
AU - Guasch, Antonio
AU - Ashley-Koch, Allison E.
AU - Telen, Marilyn J.
AU - Kutlar, Abdullah
AU - Lettre, Guillaume
AU - Papanicolaou, George J.
PY - 2013/7/18
Y1 - 2013/7/18
N2 - 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)
AB - 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)
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U2 - 10.1182/blood-2013-01-478776
DO - 10.1182/blood-2013-01-478776
M3 - Article
C2 - 23719301
AN - SCOPUS:84884621782
SN - 0006-4971
VL - 122
SP - 434
EP - 442
JO - Blood
JF - Blood
IS - 3
ER -