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Polymorphism in APOB Associated with Increased Low-Density Lipoprotein Levels in Both Genders in the General Population

Departments of Clinical Biochemistry (M.B., A.T.-H.), Medicine B (P.G.), and Vascular Surgery (H.S.), Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev University Hospital (B.G.N.), DK-2730 Herlev, Denmark; Copenhagen City Heart Study, Bispebjerg University Hospital (B.G.N., J.S.J., A.T.-H.), DK-2400 Copenhagen, Denmark; and Department of Cardiology, Gentofte University Hospital (J.S.J.), 2900 Hellerup, Denmark

Address all correspondence and requests for reprints to: Dr. Anne Tybjærg-Hansen, Department of Clinical Biochemistry, KB3011, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail: at-h{at}rh.dk.

Context: 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.

Design: 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.

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

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

Main Outcome Measures: 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.

Conclusion: 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.

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