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 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.
Talmud
P J
PJ
Centre for Cardiovascular Genetics, Dept Medicine, Royal Free and University College Medical School, London, UK. p.talmud@ucl.ac.uk
Palmen
J
J
Miller
G
G
Humphries
S E
SE
D000483:Alleles; D001055:Apolipoproteins B / Q000097:blood; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D002874:Chromosome Mapping; D017931:DNA Primers / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D006113:United Kingdom
D001055:Apolipoproteins B; D002352:Carrier Proteins; D017931:DNA Primers; D008055:Lipids; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol