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).


 * 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.
 * 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).
 * In a study of Norwegian children, nonallergic asthma was associated with rs1800629(A) carriers (odds ratio 1.7, CI: 1.3-2.3).


 * 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.


 * 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.


 * 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. []


 * 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.


 * 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).
 * 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.


 * 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.


 * 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.
 * 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.
 * A US study 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.


 * 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.


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


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


 * 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).
 * 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.


 * 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.


 * 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).


 * 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.
 * 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).


 * 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).
 * 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).