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

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Abstract
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.