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Effect of Microsomal Triglyceride Transfer Protein gene variants (−493G > T, Q95H and H297Q) on plasma lipid levels in healthy middle‐aged UK men
Author(s) -
TALMUD P. J.,
PALMEN J.,
MILLER G.,
HUMPHRIES S. E.
Publication year - 2000
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1046/j.1469-1809.2000.6440269.x
Subject(s) - microsomal triglyceride transfer protein , apolipoprotein b , triglyceride , medicine , phospholipid transfer protein , endocrinology , cholesterol , allele , microsome , genotype , phospholipid , apolipoprotein e , chemistry , biology , very low density lipoprotein , gene , lipoprotein , biochemistry , enzyme , disease , membrane
Microsomal triglyceride transfer protein (MTP) plays a central role in the synthesis of lipoproteins by shuttling lipids between phospholipid membranes 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 frequencies 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 of the variant sites were associated with significant differences in cholesterol, triglyceride, apoB or apoAI levels. When stratified by tertiles of triglycerides for the H297Q variant alone there was a significant effect on apoB levels in men in the top tertile ( p = 0.01). Considering the −493G > T and H297Q genotype in combination on baseline levels, individuals with three or four rare alleles had 6.6% higher mean apoB levels compared to the rest ( p = 0.007). Therefore, homozygosity for 297Q at higher triglyceride (Tg) levels, or in combination with −493G > T, is associated with a raising effect on apoB levels, suggesting the importance of modest differences in MTP activity in determining hepatic secretion of lipoproteins in healthy men.