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The MTP Gene Mutation in Humans

written by: Dr. Pharm Tao•edited by: Emma Lloyd•updated: 7/22/2010

The protein encoded by the MTP gene is involved in the assembly of lipoproteins. MTP gene mutation may lead to a rare disease called abetalipoproteinemia. Genetic variations of the gene have been associated with central obesity, alcoholic fatty liver disease, and cardiovascular diseases.

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    What is the MTP gene?

    The full name of the MTP gene is “microsomal triglyceride transfer protein." This gene has other symbols and is also known as ABL and MTTP. In humans, the MTP gene is located on chromosome 4.

    The protein encoded by this gene is involved in the assembly of lipoproteins. Lipoproteins are the particles in the blood that transport fats and fat-like materials such as cholesterol. The protein encoded by the MTP gene has been found in various tissues including the liver, heart, and intestines.

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    MTP gene mutation and Abetalipoproteinemia

    Deletions and missense mutations have been observed in the MTP gene, and some MTP gene mutations lead to a rare disease called abetalipoproteinemia. Patients with abetalipoproteinemia cannot make certain lipoproteins, specifically, the beta-lipoproteins. The disease is an inherited disorder with the abnormal absorption of dietary fats and fat-related substances including cholesterol and fat-soluble vitamins.

    Symptoms of abetalipoproteinemia may appear early in life, such as unable to gain weight or thrive, diarrhea, and fatty stools. Other symptoms may occur later, including the abnormal functions of the nervous system, eye disorders, and difficulties with balance and movement.

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    The MTP gene polymorphisms and other diseases

    In addition to abetalipoproteinemia, MTP gene mutations and variations have been associated with central obesity, elevated liver enzymes, and alcoholic fatty liver disease. For example, a study of 588 subjects in Korea found that the polymorphism I128T (i.e., a change of I to T at the position of 128) of the gene was significantly related to alcoholic fatty liver (Jun et al., 2009).

    Polymorphisms in the promoter region of the MTP gene may also be associated with the development of atherosclerosis and cardiovascular diseases. For instance, a study of 101 people in Japan discovered that those with the - G493T polymorphism in the promoter region had elevated levels of low-density lipoprotein and triglycerides (Okumura et al., 2009). This polymorphism has been related to increased levels of inflammatory parameters and higher risk of coronary heart disease (Gambino et al., 2007).

    Another interesting linkage was noticed among chronic hepatitis C (HCV) genotype 3-infected patients with this polymorphism (- G493T). These patients have been found to be more likely to develop fatty liver accumulation (Zampino et al., 2008). In addition, a study of 433 patients in Austria observed that the polymorphism may be connected to the pathogenesis of peripheral arterial disease (PAD) (Schgoer et al., 2008).

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    The MTP gene plays an important role in the assembly of lipoproteins and the transportation of fats. It would be very interesting to find out how MTP mutations and variations can result in those functional changes. Further studies are still needed to understand the underlying mechanisms and the potential applications in the development of novel therapeutics for these diseases.

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    Gambino, R., Bo, S., et al. (2007) Microsomal triglyceride transfer protein 493-T variant is associated with resistin levels and C-reactive protein. Clin Biochem 40, 1219-1224.

    Jun, D. W., Han, J. H., et al. (2009) Polymorphisms of microsomal triglyceride transfer protein gene and phosphatidylethanolamine N-methyltransferase gene in alcoholic and nonalcoholic fatty liver disease in Koreans. Eur J Gastroenterol Hepatol 21, 667-672.

    Okumura, K., Imamura, A., et al. (2009) Microsomal triglyceride transfer protein gene polymorphism strongly influences circulating malondialdehyde-modified low-density lipoprotein. Metabolism 58, 1306-1311.

    Schgoer, W., Eller, P., et al. (2008) The MTP -493TT genotype is associated with peripheral arterial disease: results from the Linz Peripheral Arterial Disease (LIPAD) Study. Clin Biochem 41, 712-716.

    Zampino, R., Ingrosso, D., et al. (2008) Microsomal triglyceride transfer protein (MTP) -493G/T gene polymorphism contributes to fat liver accumulation in HCV genotype 3 infected patients. J Viral Hepat 15, 740-746.