Variant "MIF:c.-270G>C"
Search results: 2 records
Variant information
Gene:
MIF 
Variant:
MIF:c.-270G>C 
Genomic location:
chr22:24236392(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_002415.1:c.-270G>C
pseudogene NR_038911.1:n.1697C>G
dbSNP ID:
rs755622  
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Altered severity(1) ,Risk factor(1)  
Details：
  • Target disease:
    Multiple Sclerosis (DOID_2377)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    P<0.01 
    Effect:
    Polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population
    Reference:
    PMID29661540
    Title:
    MIF functional polymorphisms (-794 CATT5-8 and -173 G>C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population.
    Species studied:
    Human
    Abstract:
    Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT5-8MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p<0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population.
  • Target disease:
    Multiple Sclerosis (DOID_2377)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P=4.42×10(-3) 
    Effect:
    rs755622 polymorphism in promoter region of MIF gene is associated with risk of MS and affects the promoter activity to regulate MIF expression in a sex-specific way
    Reference:
    PMID30140701
    Title:
    Genetic Variant rs755622 Regulates Expression of the Multiple Sclerosis Severity Modifier D-Dopachrome Tautomerase in a Sex-Specific Way.
    Species studied:
    Human
    Abstract:
    Multiple sclerosis (MS) is a sex-specific autoimmune disease involving central nervous system. Previous studies determined that macrophage migration inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (DDT) sex-specifically affect MS progression. Moreover, other studies reported that rs755622 polymorphism in promoter region of MIF gene is associated with risk of MS and affects the promoter activity to regulate MIF expression in a sex-specific way. Given that MIF and DDT share a part of promoter sequence, we surmise that rs755622 can also regulate DDT expression in a sex-specific way. However, this has not yet been studied. Here, we used five large-scale expression quantitative trait loci (eQTLs) and two RNA-seq datasets from brain and blood to assess the potential influence of rs755622 variant on expression of DDT in different genders by the linear regression and differential expression analysis. The results show that the minor allele frequency of rs755622 and expression of DDT are significantly increased in males for MS subjects and this minor allele variant can significantly upregulate DDT expression for males but not females, which suggests that the regulation of DDT expression level by rs755622 can affect MS progression in males. These findings further support and expand conclusions of previous studies and may help to better understand the mechanisms of MS.