{{Rsnum
|rsid=361525
|Gene=TNF
|Chromosome=6
|position=31575324
|Orientation=plus
|GMAF=0.05051
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=TNF
}}[[rs361525]] is also known as the [[TNF]]-238 SNP, and occasionally the [[rs361525]](A) allele is referred to as 238.2 (with the more common (G) allele being 238.1). This SNP in the [[tumor necrosis factor]]-alpha gene has been linked to a wide variety of conditions:

* [[Breast cancer]]
** A large study of over 5,000 Caucasian women found that [[rs361525]](A) allele carriers were at somewhat elevated risk for [[breast cancer]] compared to the (G;G) genotype, with an odds ratio per allele of 1.18, CI: 1.04-1.35, p(trend)= 0.008.{{PMID|17216494}}
** However, a 2009 European study of 30,000 breast cancer cases, compared to 30,000 controls, found no association, or as they put it, "persuasive evidence against an overall association between invasive breast cancer risk and (this SNP)". {{PMID|19423537|OA=1
}}

* [[Graft versus host disease]] (GVHD)
** A study of ~100 allogeneic haematopoietic stem cell transplant recipients in Brazil concludes that graft versus host disease (GVHD) is about twice as frequent if either the donor or the recipient is a carrier of the [[rs361525]](A) allele. {{PMID|18021367}}

* [[Otitis]] or ear infections
** Children who are [[rs361525]](G;G) homozygotes may be more prone to ear infections; adjusted odds ratio 2.29, p=0.03). {{PMID|17908769}}

* Nasal polyps
** The [[rs361525]](A;A) genotype was associated with increased risk for nasal polyps in a study of 82 Turkish patients. {{PMID|17638785}}

* [[Psoriasis]]
** A study of 160 Polish [[psoriasis]] patients indicated that the frequency of the [[rs361525]](A) allele was significantly increased (16.8% vs. 3.1%, p=0.000017, odds ratio 8.79, CI: 2.606-29.678), and furthermore, the onset age was lower in [[rs361525]](A) carriers. {{PMID|17553030}}

* [[Diabetes]] and verbal [[memory]]
** [[rs361525]](A) carriers showed a slower decline of verbal memory over a period of 48 weeks in a study of elderly patients with type-2 diabetes. {{PMID|17592954}}

* [[Sudden infant death syndrome]] (SIDS)
** [[rs361525]](G;G) babies may be at higher risk for [[sudden infant death syndrome]] (SIDS) based on a relatively small number (148) of Norwegian infants studied. {{PMID|18571009}}

* [[Exfoliation glaucoma]]
** A study of 204 patients with exfoliation glaucoma (XFG) concluded that [[rs361525]] is unlikely to be a major risk factor for XFG in Caucasians. {{PMID|19279689|OA=1
}}

* [[Lymphoma]]
**A US study {{PMID|17018637}} of 1,172 [[lymphoma]] patients and 982 controls looked at 57 SNPs in 36 immune function genes. Five SNPs in two [[cytokine]] genes, [[tumor necrosis factor]]-alpha and lymphotoxin-alpha, were associated with a 1.31x increase in [[non-Hodgkin lymphoma]] (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and with a 1.64x increase in the subtype known as [[diffuse large B cell lymphoma]] (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). The other four SNPS are listed below. The cytokine genes affect inflammatory and innate immune responses.

** [[rs1800629]]
** [[rs1799724]]
** [[rs909253]]
** [[rs2239704]]

{{ neighbor
| rsid = 1799724
| distance = 619
}}
{{ neighbor
| rsid = 1800629
| distance = 70
}}

{{PMID Auto
|PMID=18949133
|Title=Association of TNF promoter polymorphisms with type 1 diabetes in the South Croatian population
}}
{{PMID Auto
|PMID=19167443
|Title=Family-based analysis of tumor necrosis factor and lymphotoxin-alpha tag polymorphisms with type 1 diabetes in the population of South Croatia
|OA=1
}}

{{PharmGKB
|RSID=rs361525
|Name_s=TNF:-238 G/A
|Gene_s=LTA, TNF
|Feature=
|Evidence=PubMed ID:11824966; PubMed ID:16476505; PubMed ID:9528902
|Annotation=Associated with chronic infection with hepatitis B viru, the -238 GG homozygosity is associated with severe rheumatoid arthritis.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA161145120
}}

{{PMID Auto
|PMID=20157068
|Title=Association of IL1A, IL1B, and TNF Gene Polymorphisms With Chronic Rhinosinusitis With and Without Nasal Polyposis: A Replication Study
}}
{{PMID Auto
|PMID=20177654
|Title=Obesity-dependent association of TNF-LTA locus with type 2 diabetes in North Indians
}}

{{PMID Auto
|PMID=20459604
|Title=Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes
|OA=1
}}
{{PMID Auto
|PMID=20953524
|Title=Tumor necrosis factor rs361525 (-238G&gt;A) polymorphism contributes to hepatocellular carcinoma susceptibility
}}
{{PMID Auto
|PMID=21080879
|Title=A study of TNF-alpha-238 and -308 polymorphisms with different outcomes of persistent hepatitis B virus infection in China
}}

{{PMID Auto
|PMID=21447951
|Title=Association of Inflammation Genes with Alcohol Dependence/Abuse: A Systematic Review and a Meta-Analysis
}}

{{PMID Auto
|PMID=21790707
|Title=TUMOUR NECROSIS FACTOR (TNF) GENE POLYMORPHISM AND DISEASE PREVALENCE
}}

{{PMID Auto
|PMID=21904873
|Title=Association of tumor necrosis factor-? (TNF-?) promoter polymorphisms with overweight/obesity in a Korean population
}}

{{PMID Auto
|PMID=21865054
|Title=Age- and gender-specific epistasis between ADA and TNF-? influences human life-expectancy
}}

{{PMID Auto
|PMID=15726497
|Title=Gene-environment interaction effects on the development of immune responses in the 1st year of life.
|OA=1
}}

{{PMID Auto
|PMID=16449530
|Title=Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.
|OA=1
}}

{{PMID Auto
|PMID=16617143
|Title=Algorithm for automatic genotype calling of single nucleotide polymorphisms using the full course of TaqMan real-time data.
|OA=1
}}

{{PMID Auto
|PMID=16820586
|Title=Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.
|OA=1
}}

{{PMID Auto
|PMID=16846490
|Title=Lemierre's syndrome and genetic polymorphisms: a case report.
|OA=1
}}

{{PMID Auto
|PMID=16872485
|Title=Three allele combinations associated with multiple sclerosis.
|OA=1
}}

{{PMID Auto
|PMID=17174749
|Title=Linkage disequilibrium with predisposing DR3 haplotypes accounts for apparent effects of tumor necrosis factor and lymphotoxin-alpha polymorphisms on type 1 diabetes susceptibility.
|OA=1
}}

{{PMID Auto
|PMID=17327408
|Title=Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.
|OA=1
}}

{{PMID Auto
|PMID=17450233
|Title=Parental smoking modifies the relation between genetic variation in tumor necrosis factor-alpha (TNF) and childhood asthma.
|OA=1
}}

{{PMID Auto
|PMID=17668374
|Title=Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.
|OA=1
}}

{{PMID Auto
|PMID=17705862
|Title=Optimization of candidate-gene SNP-genotyping by flexible oligonucleotide microarrays; analyzing variations in immune regulator genes of hay-fever samples.
|OA=1
}}

{{PMID Auto
|PMID=17940599
|Title=Assembly of inflammation-related genes for pathway-focused genetic analysis.
|OA=1
}}

{{PMID Auto
|PMID=18194515
|Title=Polymorphisms of TNF-enhancer and gene for FcgammaRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population.
|OA=1
}}

{{PMID Auto
|PMID=18196539
|Title=TNF polymorphisms and prostate cancer risk.
}}

{{PMID Auto
|PMID=18319718
|Title=Tumour-necrosis factor-A polymorphisms and gastric cancer risk: a meta-analysis.
|OA=1
}}

{{PMID Auto
|PMID=18513389
|Title=New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
|OA=1
}}

{{PMID Auto
|PMID=18620570
|Title=The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency.
|OA=1
}}

{{PMID Auto
|PMID=18633131
|Title=Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era.
|OA=1
}}

{{PMID Auto
|PMID=18635873
|Title=TNF promoter polymorphisms associated with muscle phenotypes in humans.
|OA=1
}}

{{PMID Auto
|PMID=18676870
|Title=Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China.
|OA=1
}}

{{PMID Auto
|PMID=18698679
|Title=Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk.
|OA=1
}}

{{PMID Auto
|PMID=18713756
|Title=Association of the tumour necrosis factor-308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis.
}}

{{PMID Auto
|PMID=18715339
|Title=Associations between cytokine/cytokine receptor single nucleotide polymorphisms and humoral immunity to measles, mumps and rubella in a Somali population.
|OA=1
}}

{{PMID Auto
|PMID=18805939
|Title=Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis.
|OA=1
}}

{{PMID Auto
|PMID=18936436
|Title=Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
|OA=1
}}

{{PMID Auto
|PMID=18990758
|Title=Genetic variation in tumor necrosis factor and the nuclear factor-kappaB canonical pathway and risk of non-Hodgkin's lymphoma.
|OA=1
}}

{{PMID Auto
|PMID=19035492
|Title=Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis.
|OA=1
}}

{{PMID Auto
|PMID=19066394
|Title=Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma.
|OA=1
}}

{{PMID Auto
|PMID=19131662
|Title=A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
|OA=1
}}

{{PMID Auto
|PMID=19193698
|Title=Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate.
|OA=1
}}

{{PMID Auto
|PMID=19263529
|Title=Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.
|OA=1
}}

{{PMID Auto
|PMID=19281305
|Title=Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations.
|OA=1
}}

{{PMID Auto
|PMID=19330901
|Title=Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.
|OA=1
}}

{{PMID Auto
|PMID=19505919
|Title=Toll-like receptor signaling pathway variants and prostate cancer mortality.
|OA=1
}}

{{PMID Auto
|PMID=19559392
|Title=A candidate gene association study of 77 polymorphisms in migraine.
|OA=1
}}

{{PMID Auto
|PMID=19615068
|Title=The role of TNF genetic variants and the interaction with cigarette smoking for gastric cancer risk: a nested case-control study.
|OA=1
}}

{{PMID Auto
|PMID=19673019
|Title=IL-10 and TNF-alpha promoter haplotypes are associated with childhood Crohn's disease location.
|OA=1
}}

{{PMID Auto
|PMID=19729864
|Title=Association of genetic variation in serum amyloid-A with cardiovascular disease and interactions with IL6, IL1RN, IL1beta and TNF genes in the Cardiovascular Health Study.
|OA=1
}}

{{PMID Auto
|PMID=19732761
|Title=Tumor necrosis factor alpha (TNF-alpha) polymorphisms in Chinese patients with Graves' disease.
}}

{{PMID Auto
|PMID=20078877
|Title=Gene polymorphisms in association with emerging cardiovascular risk markers in adult women.
|OA=1
}}

{{PMID Auto
|PMID=20299531
|Title=Tumor necrosis factor-{alpha} rs361525 polymorphism is associated with increased local production and downstream inflammation in chronic obstructive pulmonary disease.
}}

{{PMID Auto
|PMID=20796230
|Title=Tumour necrosis factor-alpha gene polymorphisms and susceptibility to oral lichen planus.
}}

{{PMID Auto
|PMID=20811626
|Title=Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer.
|OA=1
}}

{{PMID Auto
|PMID=20878356
|Title=Role of ethnic variations in TNF-alpha and TNF-beta polymorphisms and risk of breast cancer in India.
}}

{{PMID Auto
|PMID=21385363
|Title=Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study.
|OA=1
}}

{{PMID Auto
|PMID=21670964
|Title=Association between TNF-alpha polymorphisms and cervical cancer risk: a meta-analysis.
}}

{{PMID Auto
|PMID=23073259
|Title=The tumor necrosis factor-α gene -238 G&gt;A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women
}}

{{GET Evidence
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs361525
|overall_frequency_n=6
|overall_frequency_d=128
|overall_frequency=0.046875
|n_genomes=4
|n_genomes_annotated=0
|n_haplomes=4
|n_articles=0
|n_articles_annotated=0
|in_pharmgkb=Y
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=22554453
|Title=Tumor necrosis factor gene variation predicts hippocampus volume in healthy individuals
}}

{{PMID Auto
|PMID=23906902
|Title=Tumor necrosis factor-308 polymorphism increases the embryo implantation rate in women undergoing in vitro fertilization
}}

{{PMID Auto
|PMID=23919499
|Title=Associations between tumor necrosis factor-alpha gene -238 G/A and -308 G/A polymorphisms and the risk of pneumoconiosis: update of a meta-analysis
}}

{{PMID Auto
|PMID=24003507
|Title=[Analysis of the -238(G/A)TNF polymorphism in breast cancer patients]
}}

{{PMID Auto
|PMID=24069456
|Title=A TNF Variant that Associates with Susceptibility to Musculoskeletal Disease Modulates Thyroid Hormone Receptor Binding to Control Promoter Activation
|OA=1
}}

{{PMID Auto
|PMID=24151497
|Title=Association Analysis of IL10, TNF-α, and IL23R-IL12RB2 SNPs with Behçet's Disease Risk in Western Algeria
|OA=1
}}

{{PMID Auto
|PMID=24160187
|Title=Meta-analysis confirms association between TNFA-G238A variant and JIA, and between PTPN22-C1858T variant and oligoarticular, RF-polyarticular and RF-positive polyarticular JIA
|OA=1
}}

{{PMID Auto
|PMID=24252077
|Title=Association of the tumour necrosis factor-α polymorphisms rs361525 and rs1800629 with susceptibility to psoriasis: a meta-analysis
}}

{{PMID Auto
|PMID=24361409
|Title=Genetic variation in TNFA predicts protection from severe bacterial infections in patients with end-stage liver disease awaiting liver transplantation
}}

{{PMID Auto
|PMID=22711844
|Title=SNPs in the TNF-alpha gene promoter associated with Behcet's disease in Moroccan patients.
}}

{{PMID Auto
|PMID=22808100
|Title=Functional differences exist between TNFalpha promoters encoding the common -237G SNP and the rarer HLA-B*5701-linked A variant.
|OA=1
}}

{{PMID Auto
|PMID=23011034
|Title=Effect of the polymorphisms of tumor necrosis factor-alpha gene on the susceptibility to primary biliary cirrhosis: a meta-analysis.
}}

{{PMID Auto
|PMID=23021043
|Title=Genetics of Behcet's disease in Sardinia: two distinct extended HLA haplotypes harbour the B*51 allele in the normal population and in patients.
}}

{{PMID Auto
|PMID=23029430
|Title=Prognostic role of host cyclooxygenase and cytokine genotypes in a Caucasian cohort of patients with gastric adenocarcinoma.
|OA=1
}}

{{PMID Auto
|PMID=23133602
|Title=Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.
|OA=1
}}

{{PMID Auto
|PMID=23590430
|Title=Genetic polymorphisms of tumour necrosis factor alpha (TNF-alpha) promoter gene and response to TNF-alpha inhibitors in Spanish patients with inflammatory bowel disease.
}}

{{PMID Auto
|PMID=23748461
|Title=Association analysis of two candidate polymorphisms in the tumour necrosis factor-alpha gene with osteoarthritis in a Chinese population.
}}

{{PMID Auto
|PMID=24905365
|Title=TNF-α gene promoter polymorphisms contribute to periodontitis susceptibility: evidence from 46 studies
}}

{{PMID Auto
|PMID=24935328
|Title=Functional tumor necrosis factor alpha polymorphisms and haplotype analysis in high-risk corneal transplantation
}}

{{PMID Auto
|PMID=25010932
|Title=Association of TNF-α, TNFRSF1A and TNFRSF1B Gene Polymorphisms with the Risk of Sporadic Breast Cancer in Northeast Chinese Han Women
}}

{{PMID Auto
|PMID=25175451
|Title=The functional VNTR of IGH enhancer HS1.2 associates with human longevity and interacts with TNFA promoter diplotype in a population of Central Italy
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}