Association of the APOLIPOPROTEIN A1/C3/A4/A5 gene cluster with triglyceride levels and LDL particle size in familial combined hyperlipidemia.

Abstract

The APOLIPOPROTEIN (APO)A1/C3/A4/A5 gene cluster on chromosome 11 has been hypothesized to be a modifier of plasma triglycerides in FCH. In the present study, we extended previous association analyses of the gene cluster to include APOA5, a newly discovered member of the cluster. Eight SNPs across the APOA1/C3/A4/A5 gene region were analyzed in 78 FCH probands and their normolipidemic spouses as well as in 27 Dutch FCH families. Of the individual SNPs tested in the case-control panel, the strongest evidence of association was obtained with SNPs in APOA1 (P=0.001) and APOA5 (P=0.001). A single haplotype defined by a missense mutation in APOA5 was enriched 3-fold in FCH probands when compared with the normolipidemic spouses (P=0.001) and a second haplotype was significantly enriched in the spouses (P=0.001). Family-based tests also indicated significant association of triglyceride levels and LDL particle size with the investigated SNPs of APOC3 and APOA5. These findings suggest that genetic variation in the APOA1/C3/A4/A5 gene cluster acts as a modifier of plasma triglyceride levels and LDL particle size within FCH families and furthermore indicate that a number of haplotypes may contribute to FCH.

• Authors: Rebecca Mar, Päivi Pajukanta, Hooman Allayee, Martine Groenendijk, Geesje Dallinga-Thie, Ronald M Krauss, Janet S Sinsheimer, Rita M Cantor, Tjerk W A de Bruin, Aldons J Lusis
• Journal: Circulation research (Circ Res) Vol. 94 Issue 7 Pg. 993-9 (Apr 16 2004) ISSN: 1524-4571 [Electronic] United States
• PMID: 15001527 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• APOA5 protein, human
• Apolipoprotein A-I
• Apolipoprotein A-V
• Apolipoprotein C-III
• Apolipoproteins
• Apolipoproteins A
• Apolipoproteins C
• Lipoproteins, LDL
• Triglycerides
• apolipoprotein A-IV

Topics

• Adult
• Alleles
• Apolipoprotein A-I (genetics)
• Apolipoprotein A-V
• Apolipoprotein C-III
• Apolipoproteins (genetics)
• Apolipoproteins A (genetics)
• Apolipoproteins C (genetics)
• Chromosomes, Human, Pair 11 (genetics)
• Female
• Gene Frequency
• Genetic Heterogeneity
• Genetic Predisposition to Disease
• Genetic Variation
• Haplotypes (genetics)
• Humans
• Hyperlipidemia, Familial Combined (blood, epidemiology, genetics)
• Linkage Disequilibrium
• Lipoproteins, LDL (chemistry)
• Male
• Middle Aged
• Multigene Family
• Mutation, Missense
• Netherlands (epidemiology)
• Particle Size
• Polymorphism, Single Nucleotide
• Risk
• Spouses
• Triglycerides (blood)