Atherosclerosis and Lipoproteins |
From the National Human Genome Research Institute (S.-H.H.J.), National Institutes of Health, Baltimore, Md; the Laboratory of Statistical Genetics (S.-H.H.J.) and the Laboratory of Biochemical Genetics and Metabolism (Z.H., J.D.S.), Rockefeller University, New York, NY; and the Department of Preventive Medicine (L.C., K.L.), Northwestern University, Chicago, Ill.
Correspondence to Kiang Liu, PhD, Department of Preventive Medicine, Northwestern University Medical School, Suite 1102, 680 N Lake Shore Dr, Chicago, IL 60611. E-mail kiangliu{at}nwu.edu
AbstractThe microsomal
triglyceride transfer protein (MTP) plays a key role in the
assembly of apolipoprotein B (apoB)-containing lipoproteins. We
investigated the relation between lipid profiles and a common
functional polymorphism (-493G/T) of the MTP gene in a large
sample of young black men in the Coronary Artery Risk
Development in Young Adults (CARDIA) Study. We performed serial
cross-sectional analyses on lipids of 586 black men in 5 exams
over 10 years of follow-up. Total cholesterol, LDL
cholesterol, and apoB levels were very similar between the
GT and GG genotypes; therefore, the GT and GG genotypes
were combined as 1 group when the 3 phenotypes were
analyzed. The results from ANCOVA showed that the TT group
(prevalence 7%) had higher levels of apoB-related lipids than did the
GT+GG group: the difference in total cholesterol ranged
from 2 (P=0.79) to 19 (P=0.002) mg/dL in
exams 1 to 5; the difference in LDL cholesterol ranged from
10 (P=0.14) to 17 (P=0.003) mg/dL in
exams 1 to 4, but in examination 5, the difference became negligible.
The TT group had higher levels of apoB, measured in only 2 exams, by 6
(P=0.12) and 9 (P=0.03) mg/dL. The TT
group had higher levels of triglycerides than did the TG or
GG group by 3 to 34 (P=0.02 to
0.003) mg/dL in all 5
exams. HDL cholesterol and apolipoprotein A-I levels were
similar among the 3 genotypes. Our serial cross-sectional
analyses indicated that the TT genotype was associated
with higher levels of total cholesterol, LDL
cholesterol, triglycerides, and apoB in young
black men. The broad effect of this polymorphism on several
atherogenic traits suggests that the MTP gene could be influential
in atherosclerosis.
Key Words: polymorphism microsomal triglyceride transfer proteins lipoproteins apolipoproteins
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