Polymorphism in APOB associated with increased low-density lipoprotein levels in both genders in the general population.
BACKGROUND
Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial.


OBJECTIVE
We tested the hypothesis that the APOB 7673C>T polymorphism (T2488T) is associated with variation in low-density lipoprotein (LDL) levels and with risk of ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD), and total mortality in the general population.


METHODS
The design was a cohort study with 22-yr follow-up (166,232 person years) and two case-control studies, The Copenhagen City Heart Study.


METHODS
The study was performed within the Danish general population and at a university hospital.


METHODS
The study was comprised of 9185 individuals from the general population, 2157 patients with IHD, and 378 patients with ICVD.


METHODS
The main outcome measures were lipids, lipoproteins, apolipoproteins (apo), IHD, ICVD, and total mortality.


RESULTS
Genotype was associated with increases in total cholesterol (women/men), LDL cholesterol, and apoB of 0.20/0.26 mmol/liter (3.3%/4.4%), 0.22/0.28 mmol/liter (5.9%/7.8%), and 5.0/5.6 mg/dl (5.9%/6.7%) in TT vs. CC homozygotes, respectively. These results were consistent over time. Despite this, the 7673C>T polymorphism was not associated with risk of IHD, ICVD, or total mortality prospectively or in case-control studies.


CONCLUSIONS
The APOB 7673C>T polymorphism is associated with moderate increases in total cholesterol, LDL cholesterol, and apoB in both genders in the general population, but not with risk of IHD, ICVD, or total mortality.
Benn
Marianne
M
Department of Clinical Biochemistry, KB3011, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
Nordestgaard
Børge G
BG
Jensen
Jan S
JS
Grande
Peer
P
Sillesen
Henrik
H
Tybjaerg-Hansen
Anne
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001055:Apolipoproteins B / Q000235:genetics*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000502:physiology*; D011153:Population; D011446:Prospective Studies
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol