Microsomal triglyceride transfer protein 493-T variant is associated with resistin levels and C-reactive protein

Background: The microsomal triglyceride transfer protein (MTP) is a heterodimeric lipid transfer protein that consists of a large unique 97-kDA subunit and protein disulfide isomerase. MTP is involved in the assembly of apoB-containing lipoprotein and enables the secretion of VLDLs by the liver and chylomicrons by the intestine. The MTP gene is highly polymorphic. The less common T variant has been associated with the reduction of plasma LDL-cholesterol levels and with an increased risk in coronary heart disease. We hypothesized that MTP polymorphism could be associated to LDL-cholesterol levels and proinflammatory cytokines, such as resistin. Methods and results: The -493G/T MTP gene polymorphism was investigated in 290 subjects. Subjects carrying the TT genotype had lower level of LDL-cholesterol and higher serum resistin levels than individual carrying one or two copies of the -493G allele. After adjustments for age, BMI, waist circumference, alcohol intake and exercise levels, a significant direct association was evident between hs-CRP and resistin levels and the presence of the TT genotype in a multiple regression model. Conclusion: This study supports the notion that the rare MTP-493T/T genotype is associated both with higher levels of inflammatory parameters and with low levels of LDL-cholesterol. Prospective data are needed to investigate if the association between CVD and the MTP-493T/T genotype might be due to the increased sub-clinical proinflammatory state associated with this mutation.