Effect of Microsomal Triglyceride Transfer Protein gene variants (-493G > T, Q95H and H297Q) on plasma lipid levels in healthy middle-aged UK men

Microsomal triglyceride transfer protein (MTP) plays a central role in the synthesis of lipoproteins by shuttling lipids between phospholipid membrane s to apoB. We have examined the effect of three MTP gene variants, -493G > T, Q95H and H297Q, in 2831 healthy UK middle-aged men. The rare allele freq uencies were: 0.25 (95 % CI 0.24-0.26) for -493T, 0.054 (95 % CI 0.05-0.06) for 95H and 0.32 (95 % CI 0.31-0.33) for 297Q. The three variants were in strong allelic association in all pairwise combinations (p < 0.001). None o f the variant sites were associated with significant differences in cholest erol, triglyceride, apoB or apoAI levels. When stratified by tertiles of tr iglycerides for the H297Q variant alone there was a significant effect on a poB levels in men in the top tertile (p = 0.01). Considering the -493G > T and H297Q genotype in combination on baseline levels, individuals with thre e or four rare alleles had 6.6% higher mean apoB levels compared to the res t (p = 0.007). Therefore, homozygosity for 297Q at higher triglyceride (Tg) levels, or in combination with -493G: > T, is associated with a. raising e ffect on apoB levels, suggesting the importance of modest differences in MT P activity in determining hepatic secretion of lipoproteins in healthy men.