alexa The APOA1 C3 A4 A5 gene cluster, lipid metabolism and cardiovascular disease risk.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Lai CQ, Parnell LD, Ordovas JM

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Abstract PURPOSE OF REVIEW: APOA1/C3/A4/A5 are key components modulating lipoprotein metabolism and cardiovascular disease risk. This review examines the evidence regarding linkage disequilibrium and haplotype structure within the A1/C3/A4/A5 cluster, and assesses its association with plasma lipids and cardiovascular disease risk. In addition, we use genomic information from several species to draw inferences about the location of functional variants within this cluster. RECENT FINDINGS: The close physical distance of these genes and the interrelated functions of these apolipoproteins have encumbered attempts to determine the role of individual variants on lipid metabolism. Therefore, current research aims to define linkage disequilibrium and haplotype structure within this cluster. Functional variants in regulatory regions are most interesting as they are potentially amenable to therapy. Comparative genomics can contribute to the identification of such functional variants. SUMMARY: Genetic variability at the APOA1/C3/A4/A5 cluster has been examined in relation to lipid metabolism and cardiovascular disease risk. However, the findings are inconsistent. This is partly due to the classic approach of studying single and mostly nonfunctional polymorphisms. Moreover, allelic expression may depend on the concurrent presence of environmental factors. Association studies using haplotypes should increase the power to detect true associations and interactions. We hypothesize that phenotypes observed in association with transcriptional regulatory variants can be readily modified by environmental factors. Therefore, studies focusing on regulatory variants may be more fruitful to locate/define future therapeutic targets.
This article was published in Curr Opin Lipidol and referenced in Journal of Proteomics & Bioinformatics

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