Variant "TNF:c.-238G>A"
Search results: 4 records
Variant information
Gene:
TNF 
Variant:
TNF:c.-238G>A 
Genomic location:
chr6:31543101(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_000594.3:c.-418G>A
protein_coding NM_000595.3:c.*1631G>A
protein_coding NM_001159740.2:c.*1631G>A
LTA-TNF:n.31543101G>A
Alias:
TNF:c.-418G>A 
dbSNP ID:
rs361525  
GWAS trait:
no data 
Modifier statisitcs
Record:
4 
Disorder:
4 
Reference:
4 
Effect type:
Expressivity(3) ,Pleiotropy(1)  
Modifier effect:
Altered life span(1) ,Altered severity(1) ,Altered stroke susceptibility(1) ,Risk factor(1)  
Details：
  • Target disease:
    Coronary Artery Disease (DOID_3393)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    High frequency 
    Effect:
    Mean frequency of the A allele of G238A was higher in Asian populations than in Caucasian populations (also in CHD patients)
    Alias in reference:
    TNF:c.-238G>A
    Reference:
    PMID28262198
    Title:
    Association of G308A and G238A Polymorphisms of the TNF-α Gene with Risk of Coronary Heart Disease: Systematic Review and Meta-analysis.
    Species studied:
    Human
    Abstract:
    It is widely acknowledged that coronary heart disease (CHD) has a genetic influence. One of the most promising candidate genes is tumor necrosis factor-alpha (TNF-α). Although there have been several positive studies associating the TNF-α gene and CHD, the evidence is not entirely consistent. The aim of the study was to evaluate the role of the TNF-α gene in CHD using combined evidence by generating a meta-analysis and a systematic review of all published data.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered life span 
    Evidence:
    P=0.022 
    Effect:
    TNFalpha-238 G/A and MBL2 O/O genotypes appear to be genetic modifiers of survival of cystic fibrosis.
    Alias in reference:
    TNF:c.-418G>A
    Reference:
    PMID17158822
    Title:
    Variants in mannose-binding lectin and tumour necrosis factor alpha affect survival in cystic fibrosis.
    Species studied:
    Human
    Abstract:
    Patients with cystic fibrosis with the same mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene differ widely in survival suggesting other factors have a substantial role in mortality.
  • Target disease:
    Nonalcoholic Fatty Liver Disease (DOID_0080208)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    P<0.0001 
    Effect:
    Associated with the development NAFLD or disease severity.
    Alias in reference:
    TNF:c.-418G>A
    Reference:
    PMID26740948
    Title:
    Genetic analysis of nonalcoholic fatty liver disease within a Caribbean-Hispanic population.
    Species studied:
    Human
    Abstract:
    We explored potential genetic risk factors implicated in nonalcoholic fatty liver disease (NAFLD) within a Caribbean-Hispanic population in New York City. A total of 316 individuals including 40 subjects with biopsy-proven NAFLD, 24 ethnically matched non-NAFLD controls, and a 252 ethnically mixed random sampling of Bronx County, New York were analyzed. Genotype analysis was performed to determine allelic frequencies of 74 known single-nucleotide polymorphisms (SNPs) associated with NAFLD risk based on previous genome-wide association study (GWAS) and candidate gene studies. Additionally, the entire coding region of PNPLA3, a gene showing the strongest association to NAFLD was subjected to Sanger sequencing. Results suggest that both rare and common DNA variations in PNPLA3 and SAMM50 may be correlated with NAFLD in this small population study, while common DNA variations in CHUK and ERLIN1, may have a protective interaction. Common SNPs in ENPP1 and ABCC2 have suggestive association with fatty liver, but with less compelling significance. In conclusion, Hispanic patients of Caribbean ancestry may have different interactions with NAFLD genetic modifiers; therefore, further investigation with a larger sample size, into this Caribbean-Hispanic population is warranted.
  • Target disease:
    Sickle Cell Anemia (DOID_10923)
    Effect type:
    Pleiotropy 
    Modifier effect:
    Altered stroke susceptibility 
    Evidence:
    A 3-way interaction test in 2 (IL4R) × 2 (TNF) × 3 (stroke subgroups) log-linear model: log likelihood ratio statistic = 6.719; degrees of freedom = 2; P=0.035. 
    Effect:
    Specific polymorphisms in the IL4R 503, TNF (-308), and ADRB2 28 genes were independently associated with stroke susceptibility in the LV stroke subgroup
    Alias in reference:
    TNF:c.-238G>A
    Reference:
    PMID14615367
    Title:
    Gene interactions and stroke risk in children with sickle cell anemia.
    Species studied:
    Human
    Abstract:
    Stroke is a devastating complication of sickle cell anemia (SCA), affecting up to 30% of children with the disease. Despite the relative frequency of stroke in SCA, few predictors of risk exist. Because stroke in SCA is likely a multifactorial disease, analysis of the combined effect of multiple genetic variants may prove more successful than evaluation of individual candidate genes. We genotyped 230 children with SCA for 104 polymorphisms among 65 candidate vascular genes to identify risk associations with stroke. Patients were phenotyped based on magnetic resonance imaging/angiography (MRI/MRA) findings into large-vessel (LV) versus small-vessel (SV) disease stroke subgroups. Specific polymorphisms in the IL4R 503, TNF (-308), and ADRB2 27 genes were independently associated with stroke susceptibility in the LV stroke subgroup, while variants in the VCAM1 (-1594) and LDLR NcoI genes were associated with SV stroke risk. The combination of TNF (-308)GG homozygosity and the IL4R 503P variant carrier status was associated with a particularly strong predisposition to LV stroke (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 2.3-13.1). We show that several candidate genes may play a role in predisposition to specific stroke subtypes in children with SCA. If confirmed, these results provide a basis for population screening and targeted intervention to prevent stroke in SCA.