title: Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B.
abstract: Renal disease is common in sickle cell anemia. In this exploratory work, we used data from a longitudinal study of the natural history of sickle cell disease to examine the hypothesis that polymorphisms (SNPs) in selected candidate genes are associated with glomerular filtration rate (GFR). DNA samples and clinical and laboratory data were available for 1,140 patients with sickle cell anemia. GFR was estimated using the Cockcroft-Gault and Schwartz formulas for adults and children, respectively. We examined approximately 175 haplotype tagging (ht) SNPs in about 70 genes of the TGFbeta/BMP pathway for their association with GFR using linear regression. Four SNPs in BMPR1B, a bone morphogenetic protein (BMP) receptor gene, yielded statistically significant associations (P values ranging from 0.015 to 0.046). Three haplotypes in this gene were also associated with GFR. The TGF-beta/BMP pathway has been associated with the development of diabetic nephropathy, which has some features in common with sickle cell nephropathy. Our results suggest that, as with other subphenotypes of sickle cell disease, renal function may be genetically modulated.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Vikki G
authors.initials: VG
authors.lastname: Nolan
authors.forename: Qianli
authors.initials: Q
authors.lastname: Ma
authors.forename: Herbert T
authors.initials: HT
authors.lastname: Cohen
authors.forename: Adeboye
authors.initials: A
authors.lastname: Adewoye
authors.forename: Anne C
authors.initials: AC
authors.lastname: Rybicki
authors.forename: Clinton
authors.initials: C
authors.lastname: Baldwin
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Mahabir
authors.forename: Erica P
authors.initials: EP
authors.lastname: Homan
authors.forename: Diego F
authors.initials: DF
authors.lastname: Wyszynski
authors.forename: Mary E
authors.initials: ME
authors.lastname: Fabry
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Nagel
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000503:physiopathology*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D004247:DNA; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I