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Experimental Genetics Group

Bolleke Abstract   Pijltje
Influence of exonic polymorphisms in the gene for LDL receptor-related protein (LRP) on risk of coronary artery disease.

Atherosclerosis. 2003 May;168(1):115-21.

Pocathikorn A1,3,4, Granath B4, Thiry E5, Van Leuven F5, Taylor R2,4, Mamotte C1*.

1Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Australia.
2Department of Cardiology, Royal Perth Hospital, Perth, Australia.
3Department of Pathology, University of Western Australia, Perth, Australia.
4Department of Medicine, University of West Australia, Perth, Australia.
5Experimental Genetics Group, LEGT EGG, Department of Human Genetics, K.U.Leuven, Leuven, Belgium. *Corresponding author.

The low density lipoprotein (LDL) receptor-related protein (LRP) is a multifunctional receptor involved in numerous biological processes relevant to vascular biology including lipoprotein metabolism. Several polymorphisms in the LRP gene have been described and in this study we examined their influence on coronary artery disease (CAD). We compared the frequencies of the exon 3 (C766T), exon 6 (C663T), exon 22 (C200T), and four rarer and more recently described polymorphisms in approximately 600 Caucasian subjects aged <50 years with angiographic CAD and approximately 700 similarly aged subjects without symptomatic CAD randomly selected from the community. We found the distribution of exon 22 C200T genotypes to differ significantly between the CAD (CC: 52%, CT: 39%, TT: 9%) and control subjects (CC: 43%, CT: 46%, TT: 11%, P=0.005), with the CC genotype conferring an odds ratio (OR) for CAD of 1.5 (95% CI: 1.2-1.8, P=0.001) despite a lack of significant influence on plasma cholesterol or triglyceride. The other LRP polymorphisms were less common. Two showed an association with CAD; for the exon 3 C766T polymorphism the TT genotype was significantly lower (1.0 vs. 2.7%; OR: 0.36; P=0.04) and, for the exon 6 C663T polymorphism, the heterozygote frequency was higher (6.2 vs. 3.4%; OR: 1.9; P=0.03) in CAD subjects. In conclusion, LRP gene polymorphisms, particularly the relatively common exon 22 C200T polymorphism, are a significant risk factor for premature CAD in Caucasians.

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