The TM6SF2 gene, or Transmembrane 6 Superfamily Member 2, is a segment of human DNA located on chromosome 19. This gene contains instructions for making a protein also named TM6SF2. Research has shown it plays a significant role in how the body handles fats, particularly within the liver.
The Role of TM6SF2 in the Body
The TM6SF2 gene and its protein product are involved in lipid metabolism, the process by which the body breaks down, transports, and stores fats. The TM6SF2 protein is primarily found in the endoplasmic reticulum and the ER-Golgi intermediate compartment of liver cells. These cellular compartments are important for processing and packaging proteins and lipids.
A key function of TM6SF2 is its influence on the secretion of very low-density lipoproteins (VLDLs) from the liver. VLDLs are a type of fat-carrying particle that transports triglycerides, a common type of fat, from the liver to other tissues in the body. The TM6SF2 protein regulates the balance between storing fat within liver cells and exporting it into the bloodstream via VLDLs. When TM6SF2 activity is reduced, the liver retains more triglycerides, leading to increased fat accumulation within liver cells, while less fat is released into the bloodstream. Conversely, increased TM6SF2 activity decreases fat accumulation in liver cells.
TM6SF2 and Liver Health
Variations in the TM6SF2 gene have a strong connection to liver health, particularly with non-alcoholic fatty liver disease (NAFLD) and its more advanced form, non-alcoholic steatohepatitis (NASH). The E167K variant (rs58542926) is a specific change in the gene that is recognized as a significant genetic risk factor for these conditions. This variant leads to an impaired function of the TM6SF2 protein.
The link between the E167K variant and NAFLD/NASH stems from the protein’s role in lipid metabolism. With the impaired function caused by the E167K variant, the liver’s ability to secrete VLDLs is reduced. This decreased secretion means that triglycerides accumulate inside liver cells rather than being efficiently transported out. Over time, this buildup of fat in the liver can lead to NAFLD, characterized by excessive fat accumulation. If inflammation and liver cell damage also occur alongside the fat accumulation, the condition progresses to NASH, which carries a higher risk of liver fibrosis and cirrhosis.
Broader Health Connections
Beyond its primary role in liver health, TM6SF2 gene variations have been linked to other health conditions. Some studies link TM6SF2 variations to cardiovascular disease. This is due to the gene’s influence on plasma lipid levels, leading to lower levels of LDL cholesterol.
The gene’s impact on lipid metabolism extends to influencing the overall balance of fats in the blood. While a variant can increase liver fat, it also influences circulating lipid levels, affecting other metabolic conditions. These broader connections highlight the complex interplay of genetic factors in metabolic health, extending beyond a single organ system.
Living with TM6SF2 Variations
For individuals with a TM6SF2 gene variation, or those concerned about their liver health, certain lifestyle adjustments can help manage potential risks. Maintaining a healthy weight through a balanced diet and regular physical activity is important. A diet that is low in saturated fats, refined carbohydrates, and sugary drinks can help reduce the fat burden on the liver.
Incorporating regular exercise, such as at least 150 minutes of moderate-intensity activity per week, can also improve metabolic health and reduce liver fat. These lifestyle modifications support overall well-being and can help mitigate the impact of genetic predispositions. Consulting with healthcare professionals for personalized advice, including specific dietary plans or exercise routines, and for accurate diagnosis and monitoring of liver health, is always recommended.