Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia

Sebastiani, Paola; Ramoni, Marco; Nolan, Vikki G.; Baldwin, Clinton T.; Steinberg, Martin H.

doi:10.1038/ng1533

Cited by 301 publications

(260 citation statements)

References 31 publications

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“…We hypothesized that these and other candidate genes might modulate the pathobiology of sickle cell disease. In previous work, we found that SNPs in some genes of this pathway were associated with sickle cell stroke, osteonecrosis, and leg ulceration [13,14]. These results led us to follow-up studies of additional genes and SNPs in the TGF-b/BMP pathway.…”

Section: Discussionmentioning

confidence: 85%

“…We and others have attributed this heterogeneity to the effects of genes that modulate the pathobiology initiated by the sickle hemoglobin (HbS) mutation [reviewed in 12]. Previously, we reported associations among genes in the TGF-b/BMP pathway with other sickle cell disease subphenotypes, including stroke, osteonecrosis, and leg ulcers [13][14][15]. The TGF-b/BMP pathway has also been implicated in the development of diabetic nephropathy [reviewed in [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B

Nolan

Cohen

et al. 2006

American J Hematol

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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 *175 haplotype tagging (ht) SNPs in about 70 genes of the TGFb/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-b/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. Am. J. Hematol. 82:179-184, 2007. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B

Nolan

Cohen

et al. 2006

American J Hematol

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“…KL, ANXA2, and BMP-6 were also shown to be associated with other vascular complications in SCD such as priapism [10] and stroke [12], suggesting a common underlying molecular basis for these vascular complications.…”

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confidence: 98%

Association of sickle avascular necrosis with bone morphogenic protein 6

et al. 2008

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“…The phenotype in patients with SCD is determined by the interaction of both genetic and environmental factors, of which some have been identified [1,[4][5][6]. It is important to increase our understanding of factors that contribute to a severe clinical course.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a pediatric severity index for sickle cell patients

et al. 2010

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There is no instrument to measure severity of sickle cell disease (SCD) in pediatric patients that is generally accepted. The aim of this study was to develop and validate a severity index for SCD in children. We developed an index consisting of 12 items and tested its validity of the index using data from 92 children. We tested whether different scores were obtained for patients classified by severity both subjectively and objectively by a partially validated existing index. Furthermore, we tested whether the index could differentiate patients classified according to genotype or the number of a-gene deletions and evaluated whether the score on the index was correlated with the average number and days of hospitalizations/year, age and a risk of death score. We explored the effect of three different weighting systems (Score A, B, and C) to summarize these items. All weightings demonstrated a significant difference between the scores of mild, moderate, and severely affected patients, as classified by a subjective rating or with an existing index (P < 0.01). The index clearly differentiated patients by genotype (P < 0.01) or a-gene deletions (P < 0.01). The correlation with hospitalization was moderate. Age and the risk of death score were weakly associated with the pediatric severity index for SCD. This is the first pediatric SCD severity index that was developed and validated using modern clinimetric methodology. The validity and reliability of this index should be further evaluated in a prospective study including a larger cohort, preferably diagnosed at birth. Am. J. Hematol. 85:746-751, 2010. V

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Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia

Cited by 301 publications

References 31 publications

Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B

Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B

Association of sickle avascular necrosis with bone morphogenic protein 6

Development and validation of a pediatric severity index for sickle cell patients

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