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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Common genomic variation in the APOC3 promoter associated with variation in plasma lipoproteins.

We hypothesized that common genomic variation that affected the expression and/or function of the products of the APOC3, APOE, FABP2, and PON1 genes would be associated with variation in biochemical phenotypes in a previously unstudied human sample. We determined genotypes of functional genomic variants of APOC3, APOE, FABP2, and PON1 in 509 adult aboriginal Canadians from an isolated community in Northern Ontario. We tested for genotype associations with plasma lipoprotein traits. We found that (1) common variation at nucleotide -455 of the APOC3 promoter was associated with variation in plasma triglycerides (P = .006) and (2) common variation of APOE determining plasma isoforms of apo E was associated with variation in plasma apo B (P = .009). Analysis of subjects classed by APOC3 markers showed that homozygosity for presence of a C at nucleotide -455 and a T at nucleotide -482 was associated with significantly increased plasma triglycerides in both men and women. Furthermore, this allele was approximately twice as frequent in subjects within the highest quartile of plasma triglycerides as in subjects within the lowest quartile. Since the DNA variation detected by the APOC3 markers affects in vitro expression of the gene product, it is possible that the marker itself caused the associations. However, the associations could also have resulted from linkage disequilibrium with other functional variants in APOC3 or the closely linked APOA1 and/or APOA4 genes.[1]


  1. Common genomic variation in the APOC3 promoter associated with variation in plasma lipoproteins. Hegele, R.A., Connelly, P.W., Hanley, A.J., Sun, F., Harris, S.B., Zinman, B. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
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