Rs1800629

This SNP in the tumor necrosis factor-alpha gene, rs1800629, is also known as the TNF-308 SNP. Occasionally the rs1800629(A) allele is referred to as 308.2 or TNF2, with the more common (G) allele being 308.1 or TNF1. The (A) allele is associated with higher levels of TNF expression. This SNP has been linked to a wide variety of conditions:

• Allograft rejection
  • Among 72 Polish patients receiving a kidney transplant, the risk of acute kidney allograft rejection was 2.5x higher among rs1800629(A) carriers compared to (G;G) homozygotes (CI: 1.19- 5.37, p<.05). [PMID 15964333]

• Asthma
  • A meta-analysis of ~2,500 patients combined indicated that the rs1800629(A) allele was associated with a 1.46x increased risk for asthma. [PMID 16865291]
  • In a study of ~600 Mexican families and their asthmatic children, rs1800629(A) carriers had an increased risk of asthma (relative risk = 1.54, CI: 1.04-2.28), especially among children of non-smoking parents (odds then 2.06, CI: 1.19-3.55, p for interaction = 0.09). [PMID 17450233]
  • In a study of Norwegian children, nonallergic asthma was associated with rs1800629(A) carriers (odds ratio 1.7, CI: 1.3-2.3). [PMID 17686102]

• Chronic obstructive pulmonary disease
  • A meta-analysis of 36 publications totaling ~5,000 patients concluded that the association between the rs1800629(A) allele and the risk of COPD was statistically significant for Asians (odds ratio 2.36, CI: 1.84 - 3.02, p < 0.0001) but not for Caucasians.[PMID 20946339]

• Crohn's disease
  • In a study of 235 Portuguese patients, the rs1800629(A;A) genotype was associated with higher susceptibility to Crohn's disease, with an odds ratio of 3.0 (CI: 1.2-7.2). These homozygotes also showed more disease-related complications. [PMID 15803022]

• Exfoliation glaucoma (XFG)
  • A study of 204 patients with exfoliation glaucoma (XFG) concluded that rs1800629 is unlikely to be a major risk factor for XFG in Caucasians. PMID 19279689

• Graves' disease
  • A meta-analysis of 10 case-control studies, including over 2,200 Graves' disease cases, concluded that rs1800629(A) carriers were associated with this type of hyperthyroidism. [PMID 18472000]

• Heart disease
  • A study of 600 Italian patients concluded that rs1800629(A) carriers are at increased risk for acute heart attack and have other markers of heart disease. The odd ratio was 1.86, CI: 1.08-3.21, p=0.027). [PMID 16319659]
  • A study of 50 Egyptian children with rheumatic heart disease found increased risk associated with the rs1800629(A;A) homozygotes, with odds ratio = 5.7, p<0.001. However, there was a significantly lower frequency of heterozygous genotypes. [PMID 17607501]

• Leprosy
  • A study of 37 Thai patients with leprosy found that the rs1800629(A) allele was more common (odds ratio = 2.69, p=0.04). [PMID 17624216}

• Liver disease
  • A study of 108 Chinese patients concludes that rs1800629(A) carriers are at 3.23x (CI: 1.10-9.44) increased risk for liver cancer and are also at higher risk for hepatic fibrosis and more severe liver damage. [PMID 18030367]

• Lymphoma
  • A study of 194 Tunisian patients indicated an increased risk for non-Hodgkin lymphoma among rs1800629(A;A) genotypes, at an odds ratio of 3.63, p=0.028. [PMID 17087739]
  • A study of 441 incident non-Hodgkin lymphoma (NHL) cases indicated that, compared with the wild-type rs1800629(G;G), the (A;A) genotype was associated with increased risk (odds ratio 2.14, CI: 0.94-4.85), whereas the (A;G) genotype was not. This association was similar for follicular lymphoma and diffuse large B-cell lymphoma. [PMID 18990758]
  • 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.
    • rs361525
    • rs1799724
    • rs909253
    • rs2239704

• Susceptibility to Mediterranean spotted fever
  • Although cytokine genes affect immune response to infection, in a Sicilian population the rs1800629 polymorphism did not affect susceptibility to Mediterranean spotted fever. [PMID 19386798]

• Migraine
  • Polymorphisms in the tumor necrosis factor (TNF) gene may be associated with migraine and cardiovascular disease. The rs1800629 SNP has not been found significant. [PMID 19559392]

• Multiple sclerosis (MS)
  • A study of 300 Croatian and Slovenian patients indicated that rs1800629(A) carriers might be at lower risk for multiple sclerosis. [PMID 17268200]

• Nasal polyps
  • The rs1800629(A;G) genotype was associated with increased risk for nasal polyps in a study of 82 Turkish patients. [PMID 17638785]
  • Another study found a nearly doubled risk for rs1800629(A) carriers (odds ratio, 1.86; confidence interval, 1.4-3.09). [PMID 19405090]

• Psoriasis
  • A study of 160 Polish patients indicated that the rs1800629(A) allele frequency was significantly decreased among patients with early-onset psoriasis (7.5% vs. 15.4%, p=0.022). [PMID 17553030]
  • In contrast, 147 Irish patients with psoriasis were studied and the results indicated that the rs1800629(A;A) genotype was associated with increased risk as well as earlier onset of psoriasis. [PMID 12746914]

• Rheumatoid arthritis - response to TNF-alpha inhibitors
  • 2009 meta-analysis of 9 studies concludes rs1800629(A) allele carriers respond less well to TNF-alpha inhibitors when being treated for rheumatoid arthritis. [PMID 19365401]

• Sarcoidosis
  • In a pooled analysis of seven case-control studies, the odds ratio for sarcoidosis for carriers of the rs1800629(A) allele was either 1.47 (CI 1.03-2.08 under a dominant model) or 1.39 (CI: 0.67-2.90; under a recessive model). [PMID 17768594]

• Susceptibility to sepsis
  • A study of 159 patients with severe trauma indicated that the rs1800629(A) allele was associated with higher risk of developing sepsis and of dying (odds ratio 7.65, two-sided p = 1.9 x 10^-6). The authors of this research suggest that preemptive anti-inflammatory interventions should be developed for use in carriers of this SNP should they suffer severe injuries. [PMID 18434886]
  • A meta-analysis of 25 studies concluded that while rs1800629 status is significantly associated with risk for sepsis, especially among Asians, it was not associated with mortality from sepsis. However, there may be an increased risk for fatal outcomes among Asians (odds ratio 10.75, CI: 3-39, p < 0.01).[PMID 19789454]

• Systemic lupus erythematosus (SLE)
  • A study of 120 Columbian patients with SLE found an increased risk for rs1800629(A) carriers (odds ratio 3.9, CI: 1.65-5.80, p= 0.0004). [PMID 17711410]
  • A meta-analysis of 21 studies indicated that in European populations, the rs1800629(A) allele is associated with increased risk for systemic lupus erythematosus (SLE). In Europeans, the oodds ratio for the (A;A) genotype was 4.0, CI: 2.5-6.4, p<0.001. No association was detected in Asian-derived populations. The overall odds ratio for rs1800629(A) carriers was 2.0 (CI: 1.3-3.1, p<0.001). [PMID 16418737]

[PMID 19419979] Preliminary Evidence of a Genetic Association Between Tumor Necrosis Factor Alpha and the Severity of Sleep Disturbance and Morning Fatigue

[PMID 19654554] The Major Histocompatibility Complex Conserved Extended Haplotype 8.1 in AIDS-Related Non-Hodgkin Lymphoma

[PMID 19167443] Family-based analysis of tumor necrosis factor and lymphotoxin-alpha tag polymorphisms with type 1 diabetes in the population of South Croatia

[PMID 19233472] Long-range linkage on chromosome 6p of VEGF, FKBP5, HLA and TNF alleles associated with transplant rejection

[PMID 20132806] Study of TNFalpha -308 G/A and IL6 -174 G/C polymorphisms in type 2 diabetes and obesity risk in the Tunisian population

[PMID 20157068] Association of IL1A, IL1B, and TNF Gene Polymorphisms With Chronic Rhinosinusitis With and Without Nasal Polyposis: A Replication Study

[PMID 19773451] Role of inflammation gene polymorphisms on pain severity in lung cancer patients

[PMID 20177654] Obesity-dependent association of TNF-LTA locus with type 2 diabetes in North Indians

[PMID 20080841] Additive effect of polymorphisms in the IL-6, LTA, and TNF-{alpha} genes and plasma fatty acid level modulate risk for the metabolic syndrome and its components

[PMID 20357201] Association of Polymorphisms of Tumor Necrosis Factor and Tumor Protein p53 with Primary Open Angle Glaucoma: A Replication Study of Ten Genes in A Chinese Population

[PMID 20522203] Age- and gender-specific association between ADA (22G>A) and TNF-alpha (-308G>A) genetic polymorphisms

[PMID 20459604] Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes

[PMID 20578265] Carriage of a tumor necrosis factor polymorphism amplifies the cytotoxic T-lymphocyte antigen 4 attributed risk of primary biliary cirrhosis: Evidence for a gene-gene interaction

[PMID 20682333] Associations between the TNF-alpha gene (-308G-->A) and event-related potential indices of attention and mental rotation

[PMID 20087644] Genetic variation in chromosomal translocation breakpoint and immune function genes and risk of non-Hodgkin lymphoma

[PMID 20946339] Association between the tumour necrosis factor-? -308G/A polymorphism and chronic obstructive pulmonary disease: An update

[PMID 21080879] A study of TNF-alpha-238 and -308 polymorphisms with different outcomes of persistent hepatitis B virus infection in China

[PMID 21137202] [Polymorphism of cytokine genes and human longevity]

[PMID 20693638] An association study of 21 potential Alzheimer's disease risk genes in a Finnish population

[PMID 21291465] The association of genetic polymorphisms with cerebral palsy: a meta-analysis

[PMID 21447951] Association of Inflammation Genes with Alcohol Dependence/Abuse: A Systematic Review and a Meta-Analysis

[PMID 21450487] Tumor necrosis factor-? -863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery

[PMID 21609779] Association of TNF-? and IL-10 polymorphisms with tuberculosis in Tunisian populations

[PMID 21790707] TUMOUR NECROSIS FACTOR (TNF) GENE POLYMORPHISM AND DISEASE PREVALENCE

[PMID 21357384] Polymorphisms in the TNF-? and IL10 gene promoters and risk of arsenic-induced skin lesions and other nondermatological health effects

[PMID 21995493] TNFRSF1B +676 T>G polymorphism predicts survival of non-Small cell lung cancer patients treated with chemoradiotherapy

[PMID 22031281] Preferential transmission of genetic risk variants of candidate loci at 6p21 from asymptomatic grandparents to mothers of children with neonatal lupus

[PMID 22043116] A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis

[PMID 21865054] Age- and gender-specific epistasis between ADA and TNF-? influences human life-expectancy

[PMID 22475653] Genetic predictors of fatigue in prostate cancer patients treated with androgen deprivation therapy: Preliminary findings

[PMID 22568453] Association of CASP3 polymorphism with hematologic toxicity in advanced NSCLC patients treated with platinum-based chemotherapy