Gene "MAP2K1"
Found 2 records
Gene information
Gene symbol:
MAP2K1
See related:
Ensembl: ENSG00000169032, Gene ID: 5604
Additive variants :
Detected
Genetic interaction partners
No data
Modifier statisitcs
Record:
2 
Disorder:
1 
Vriant:
2 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Altered HbF levels(1) ,Risk factor(1)  
Details：
  • Variant 1:
    MAP2K1:c.81-16471G>A
    Gene:
    MAP2K1
    Genomic location:
    chr15:66710894
    dbSNP ID:
    rs4489951
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 2:
    MAP2K1:c.438+2055G>C
    Gene:
    MAP2K1
    Genomic location:
    chr15:66731285
    dbSNP ID:
    rs8036023
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    OR=2.63, 95% CI: (1.04 – 6.67), P= 0.0414 
    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.