Variant "TGFBR2:c.529+4864T>C"
Search results: 2 records
Variant information
Gene:
TGFBR2 
Variant:
TGFBR2:c.529+4864T>C 
Genomic location:
chr3:30696816(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_001024847.2:c.529+4864T>C
protein_coding NM_003242.5:c.454+4864T>C
dbSNP ID:
rs1019856  
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
2 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Risk factor(2)  
Details：
  • Target disease:
    Necrosis (EFO_0009426)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    Bone morphogenic protein 6, annexin A2, and klotho were associated with sickle cell osteonecrosis and at high risk for osteonecrosis.
    Reference:
    PMID15784727
    Title:
    Association of klotho, bone morphogenic protein 6, and annexin A2 polymorphisms with sickle cell osteonecrosis.
    Species studied:
    Human
    Abstract:
    In patients with sickle cell disease, clinical complications including osteonecrosis can vary in frequency and severity, presumably due to the effects of genes that modify the pathophysiology initiated by the sickle mutation. Here, we examined the association of single nucleotide polymorphisms (SNPs) in candidate genes (cytokines, inflammation, oxidant stress, bone metabolism) with osteonecrosis in patients with sickle cell disease. Genotype distributions were compared between cases and controls using multiple logistic regression techniques. An initial screen and follow-up studies showed that individual SNPs and haplotypes composed of several SNPs in bone morphogenic protein 6, annexin A2, and klotho were associated with sickle cell osteonecrosis. These genes are important in bone morphology, metabolism, and vascular disease. Our results may provide insight into the pathogenesis of osteonecrosis in sickle cell disease, help identify individuals who are at high risk for osteonecrosis, and thus allow earlier and more effective therapeutic intervention.
  • Target disease:
    Sickle Cell Anemia (DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    OR=2.05, 95% CI: (1.14 – 3.72), P= 0.0170 
    Effect:
    The TGF-beta/BMP signalling pathway modulates wound healing and angiogenesis, among its other functions.
    Reference:
    PMID16681647
    Title:
    Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/BMP pathway.
    Species studied:
    Human
    Abstract:
    Cutaneous leg ulcers are common in sickle cell anaemia and their risk might be genetically determined. Sickle cell anaemia patients were studied to examine the relationship of leg ulcers with haemolysis and with single nucleotide polymorphisms (SNPs) in candidate genes that could affect sickle vasoocclusion. Leg ulcer patients had lower haemoglobin levels and higher levels of lactate dehydrogenase, bilirubin, aspartate transaminase and reticulocytes than did control patients with sickle cell anaemia but without leg ulcers. Age-adjusted comparisons showed that sickle cell anaemia-alpha thalassaemia was more frequent among controls than cases. These results strongly suggested that the likelihood of having leg ulcers was related to the intensity of haemolysis. 215 SNPs in more than 100 candidate genes were studied. Associations were found with SNPs in Klotho, TEK and several genes in the TGF-beta/BMP signalling pathway by genotypic association analyses. KL directly or indirectly promotes endothelial nitric oxide (NO) production and the TEK receptor tyrosine kinase is involved in angiogenesis. The TGF-beta/BMP signalling pathway modulates wound healing and angiogenesis, among its other functions. Haemolysis-driven phenotypes, such as leg ulcers, could be improved by agents that reduce sickle erythrocyte density or increase NO bioavailability.