title: Microsomal triglyceride transfer protein gene polymorphism strongly influences circulating malondialdehyde-modified low-density lipoprotein.
abstract: Microsomal triglyceride transfer protein (MTP) plays a critical role in the assembly of lipoproteins. Therefore, we studied whether MTP gene polymorphisms are associated with atherosclerosis-promoting parameters, especially metabolic profiles and endothelial function, in healthy young men. One hundred one healthy men (mean age, 30.3 years) were studied. We analyzed the 2 promoter polymorphisms (-493G/T and -400A/T) of the MTP gene. Linkage disequilibrium analysis revealed a significant but incomplete linkage disequilibrium between the 2 polymorphisms (D' = 0.74). The -493T allele carriers (n = 26) showed marked increases in their levels of malondialdehyde-modified low-density lipoprotein (mean value, 135 vs 99 U/L in the G/G carriers; P = .003) and triglycerides (2.15 vs 1.16 mmol/L, P = .014), and reduced low-density lipoprotein particle size (259.2 vs 264.3 nm, P = .023), whereas there was no difference in apolipoproteins, insulin, adiponectin, homocysteine, folate, and endothelial function assessed using ultrasound measurement of brachial artery flow-mediated vasodilation. In contrast, the -400T allele carriers (n = 61) showed a reduced endothelial function (P = .044), accompanied by elevated apolipoprotein B levels in subjects with higher triglyceride levels. These results indicate that both promoter polymorphisms may be associated with the development of atherosclerosis and cardiovascular diseases, but that the mechanism responsible may be different.
authors.affiliation: Cardiovascular Research Medicine, Nagoya University School of Medicine, Nagoya 466-8550, Japan. kenji@med.nagoya-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Okumura
authors.forename: Akiko
authors.initials: A
authors.lastname: Imamura
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Murakami
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Takahashi
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Numaguchi
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D001054:Apolipoproteins A / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D002352:Carrier Proteins / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000031:analogs & derivatives* / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D054392:Adipokines; D001054:Apolipoproteins A; D002352:Carrier Proteins; D008077:Lipoproteins, LDL; D014280:Triglycerides; C502964:malondialdehyde-low density lipoprotein, mouse; C106092:microsomal triglyceride transfer protein; D008315:Malondialdehyde