title: Haplotype analysis of the apolipoprotein gene cluster on human chromosome 11.
abstract: Members of the apolipoprotein gene cluster (APOA1/C3/A4/A5) on human chromosome 11q23 play an important role in lipid metabolism. Polymorphisms in both APOA5 and APOC3 are strongly associated with plasma triglyceride concentrations. The close genomic locations of these two genes as well as their functional similarity have hindered efforts to define whether each gene independently influences human triglyceride concentrations. In this study, we examined the linkage disequilibrium and haplotype structure of 49 SNPs in a 150-kb region spanning the gene cluster. We identified a total of five common APOA5 haplotypes with a frequency of greater than 8% in samples of northern European origin. The APOA5 haplotype block did not extend past the 7 SNPs in the gene and was separated from the other apolipoprotein gene in the cluster by a region of significantly increased recombination. Furthermore, one previously identified triglyceride risk haplotype of APOA5 (APOA5*3) showed no association with three APOC3 SNPs previously associated with triglyceride concentrations, in contrast to the other risk haplotype (APOA5*2), which was associated with all three minor APOC3 SNP alleles. These results highlight the complex genetic relationship between APOA5 and APOC3 and support the notion that APOA5 represents an independent risk gene affecting plasma triglyceride concentrations in humans.
authors.affiliation: Human and Molecular Genetics Center, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. molivier@mcw.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Olivier
authors.forename: Xujing
authors.initials: X
authors.lastname: Wang
authors.forename: Regina
authors.initials: R
authors.lastname: Cole
authors.forename: Brian
authors.initials: B
authors.lastname: Gau
authors.forename: Jessica
authors.initials: J
authors.lastname: Kim
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
mesh_terms: D001053:Apolipoproteins / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D005810:Multigene Family / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics
chemical_list: D001053:Apolipoproteins