Severe sickle cell anemia is associated with increased plasma levels of TNF-R1 and VCAM-1.
Sickle cell anemia (SCA, HBB glu6val) is characterized by multiple complications and a high degree of phenotypic variability: some subjects have only sporadic pain crises and few acute hospitalizations, while others experience multiple serious complications, high levels of morbidity, and accelerated mortality [1]. The tumor necrosis factor-α (TNF-α) signaling pathway plays important roles in inflammation and the immune response; variation in this pathway might be expected to modify the overall severity of SCA through the pathway's effects on the vascular endothelium [2,3]. We examined plasma biomarkers of TNF-α activity and endothelial cell activation for associations with SCA severity in 24 adults (12 mild, 12 severe). Two biomarkers, tumor necrosis factor-α receptor-1 (TNF-R1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in subjects with severe SCA. Along with these biomarker differences, we also examined data from a genome-wide association study (GWAS) using SCA severity as a disease phenotype, and found evidence of genetic association between disease severity and a single nucleotide polymorphism (SNP) in VCAM1, which codes for VCAM-1, and several SNPs in ARFGEF2, a gene involved in TNF-R1 release [4].
Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Daniel A
DA
Dworkis
Elizabeth S
ES
Klings
Nadia
N
Solovieff
Guihua
G
Li
Jacqueline N
JN
Milton
Stephen W
SW
Hartley
Efthymia
E
Melista
Jason
J
Parente
Paola
P
Sebastiani
Martin H
MH
Steinberg
Clinton T
CT
Baldwin
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000235:genetics / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D055106:Genome-Wide Association Study; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012720:Severity of Illness Index; D014481:United States; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood* / Q000235:genetics
C119088:ARFGEF2 protein, human; D015415:Biomarkers; D020662:Guanine Nucleotide Exchange Factors; D047888:Receptors, Tumor Necrosis Factor, Type I; D019010:Vascular Cell Adhesion Molecule-1
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