title: Association of polymorphisms of IGF1R and genes in the transforming growth factor- beta /bone morphogenetic protein pathway with bacteremia in sickle cell anemia.
abstract: Infection and bacteremia are common in sickle cell disease. We hypothesized that, consistent with evidence for the genetic modulation of other disease complications, the risk of developing bacteremia might also be genetically modulated. Accordingly, we studied the association of single nucleotide polymorphisms (SNPs) in candidate genes with the risk of bacteremia in sickle cell anemia. We found significant associations with SNPs in IGF1R and genes of the TGF-beta /BMP pathway (BMP6, TGFBR3, BMPR1A, SMAD6 and SMAD3). We suggest that both IGF1R and the TGF-beta /BMP pathway could play important roles in immune function in sickle cell anemia and their polymorphisms may help identify a "bacteremia-prone" phenotype.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Adeboye H
authors.initials: AH
authors.lastname: Adewoye
authors.forename: Vikki G
authors.initials: VG
authors.lastname: Nolan
authors.forename: Qianli
authors.initials: Q
authors.lastname: Ma
authors.forename: Clinton
authors.initials: C
authors.lastname: Baldwin
authors.forename: Diego F
authors.initials: DF
authors.lastname: Wyszynski
authors.forename: John J
authors.initials: JJ
authors.lastname: Farrell
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000235:genetics; D016470:Bacteremia / Q000150:complications* / Q000235:genetics*; D055418:Bone Morphogenetic Protein 6; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051905:Smad6 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; C497802:SMAD6 protein, human; D051900:Smad3 Protein; D051905:Smad6 Protein; D016212:Transforming Growth Factor beta; C071736:betaglycan; D017526:Receptor, IGF Type 1; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I