Tumour Necrosis Factor-α
TNFA -308 G>A
Allele frequency in the general population: A allele = 9%
Gene and SNP Summary
Tumour necrosis factor-α (TNFα) is a proinflammatory cytokine secreted by both macrophages and adipocytes and has been implicated in the development of diseases of lifestyle including obesity related insulin resistance and dyslipidaemia as well as some autoimmune diseases. The TNFA -308 G/A SNP, specifically the GA and AA genotypes have been associated with increased risk of diseases of lifestyle, especially when exposed to an unfavourable environment. Specific interventions to negate the risk of the SNP include achieving and maintaining a healthy weight and fat percentage, avoidance of smoking, and moderating fat intake – emphasising an increased intake of omega 3 fatty acids.
TNFα Gene Detail
Tumour necrosis factor-α (TNFα) is a potent pro-inflammatory and immunoregulatory cytokine that is predominantly produced by monocytes and macrophages. The gene is found in the Human Leukocyte Antigen (HLA) III region on chromosome 6 (6p21.31) and spans about 3 kb and contains 4 exons.
TNFα is responsible for the activation of a number of other cytokines and mediates the cytokine cascade that causes inflammation. Among the first genes activated by any initiating factor (any challenge to a tissue) are the genes IL-1 and TNFα. Both these molecules are capable of activating each other and are critical components of the inflammatory process. TNFα induces migration, proliferation, and apoptosis, and is also involved in immune responses.
TNFα expression has been shown to be upregulated in adipose tissue and is increased in the serum of ageing patients as well as those with obesity. Both the pro-inflammatory and the proapoptotic actions of TNFα are largely mediated through Tumour Necrosis Factor Receptor 1 (TNFR1). In contrast, Tumour Necrosis Factor Receptor 2 (TNFR2) mediates the activation of the protective pathway and is believed to promote tissue repair and angiogenesis.
TNF -308 G>A
The TNFα -308 G/A SNP is found in the promoter region of the gene and results in an increase in the expression of this pro-inflammatory cytokine. The SNP has been associated with increased risk of cardiovascular disease and obesity related insulin resistance, periodontitis, as well as certain cancers and autoimmune diseases and acne. The TNFα -308 A allele may also be used as a possible predictor of elevated TNFA levels in patients with sepsis.
In a study by Huang et al. investigating the effects of the SNP on TNFA levels and heavy metal exposure, the A allele was associated with increased levels of TNFA especially in the presence of lead exposure, but there was also an interaction between copper and lead, which decreased TNFA levels.
- Achieve and maintain a healthy weight and fat percentage due to the impact of increasing adiposity on inflammation.
- Avoid smoking.
- Increase intake of omega 3 fatty acids. If the dietary intake of omega 3 fatty acids is inadequate, supplementation may be required. Fish oil supplementation was found to be more effective at suppressing TNFα in GA individuals than GG individuals according to Grimble et al. (2002).
- Reduce saturated fatty acids and trans fat intake.
- Engage in regular, moderate physical activity.
- A high sensitivity CRP blood test may give further insight in at risk individuals.
Expression and Sequence Variants of Inflammatory Genes; Effects on Plasma Inflammation Biomarkers Following a 6-Week Supplementation with Fish Oil
Cormier et al, 2016.