Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B. 1703 27

Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who had been screened for pHTN by echocardiography (n = 111). Evidence of association was primarily identified for genes in the TGFbeta superfamily, including activin A receptor, type II-like 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGFbeta pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the beta-1 adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6, and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets, and reducing the occurrence of this life-threatening SCD complication.
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PMID:Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. 1854 90

BMP-SMAD (bone morphogenetic protein) signaling pathways in association with APT play paramount roles in osteoblastic differentiation, bone formation and embryonic development of human and animals. However, the implications of potent components (BMP6, Smad1, Smad2 and APT) of this pathway in SCD (sickle cell disease) pathology with orthopedic complications (Ortho+SS) are poorly elucidated and substantially unknown. Here, we address the role of BMP6, Smad1, Smad2 and APT mRNA and protein expression in hMDDCs obtained from Ortho+SS patients, employing RT-PCR, qRT-PCR and immunoblotting. Interestingly, we observed that SCD pathology exhibited significantly up-regulated expression of those signaling components at the level of mRNA and protein. Furthermore, exogenous BMP6 induced apoptosis was observed to be significantly associated in Ortho+SS complication and markedly increased the percentage of cells undergoing apoptosis as compared to healthy group. Interestingly, the non-stimulated cells have shown higher apoptotic nuclei percentage than the stimulated cells in pathological condition. Thus, expression of BMP-SMAD signaling components augments apoptosis and up regulates the transcription of these genes and it suggests that induction is due to transcriptional regulation. Taken together, our findings provide evidence that BMP-SMAD signaling components along with APT were over expressed, mediates apoptosis and may play an important role in the SCD pathology with orthopedic complications.
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PMID:Induced expression of bone morphogenetic protein-6 and Smads signaling in human monocytes derived dendritic cells during sickle-cell pathology with orthopedic complications. 2046 Jan 5