Association Of MTP Polymorphisms With Hyperlipidemia And Non-alcoholic Fatty Liver

Background: The liver is a vital organ in lipid metabolism. The disorder in entering or excreting of lipids from liver can cause lipids deposit in periphery or in the liver which may result in related diseases such as hyperlipidemia or non-alcoholic fatty liver. Microsomal triglyceride transfer protein(MTP) is an important transporter in assembling and secreting of VLDL. MTP plays a crucial role in keeping very low density lipoprotein excreting from the liver normally. Recently, It was indicated that MTP -164T/C polymorphism may influence the function of MTP, thus may have influence on lipid metabolism and related diseases.Aims: Our aim is to investigate the possible role of MTP -164T/C polymorphism in modulating susceptibility of hyperlipidemia and non-alcoholic fatty liver(NAFLD).Methods: During September 2007 to November 2008, from The Third Xiangya Hospital Of Central-south University Health Manager Center, We analyzed 452 subjects involved hyperlipidemic subjects and the age sex matched controls and 439 subjects involved patients with non-alcoholic fatty liver and the age sex matched controls . Case history, anthropometric indexes, lipids profiles, blood pressure, fasting blood glucose, liver function were collected. MTP -164C genotype were obtained using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method. ANOVA, chi square, logistic regression et al had been used to analyze the associations in both genders. P < 0.05 is thought to be significant.Results: The frequency of MTP -164C allele in Chinese is 16.7%, which is significant lower than the frequency in Swedes (24%), English (24.7%), French (29.6%) (P < 0.01). These indicate the frequencies of these genotypes may have racial difference. The frequency of MTP -164C in hyperlipidemia is 14.0%, significantly lower than in the controls 19.0% (P < 0.05), while in NAFLD is 19.6%, which is higher than in the controls 13.7% (P < 0.05). In males, Individuals with MTP -164C and individuals owning -164T allele 's total cholesterol concentration is 5.1±0.9,4.8±0.9 (P < 0.05) respectively; the concentration of LDL-C is 3.05±0.85,2.84±071 (P < 0.05)respectively. But no association between this genotype and any traits of metabolic syndrome in females were find. We additionally use logistic regression to analyze the gene polymorphism with disease risks in two studies enrolling the hyperliipidemia and NAFLD. The MTP -164C virant may protect to suspect hyperiipidemia (OR=0.66, 95% CI: 0.45-0.96, P=0.03), while may be a susceptibility factor for NAFLD (OR=1.62, 95% CI:1.10-2.38, P=0.01).Conclusions: 1. The frequency of MTP -164T/C mutant may have racial difference, lower than western populations. 2. In men, MTP -164T/C polymorphism may influence the levels of some lipids and related indexes. 3. Subjects owning the -164C allele seem to protect against hyperlipidemia while prone to non-alcoholic fatty liver than these who own the -164T allele.