出版社：American Society for Biochemistry and Molecular Biology
摘要：Linkage and association between the apolipoprotein (apo) A-I/C-III/A-IV gene region on chromosome 11 and familial combined hyperlipidemia (FCHL) has been observed previously. Using sequence analysis two new allelic variants were identified, C317-T in intron 2 of the apoA-I gene and C1100-T in exon 3 of the apoC-III gene. These variants were studied in 30 FCHL probands, 159 hyperlipidemic relatives, 327 normolipidemic relatives, and 218 spouses. The allele frequencies of both variants were significantly different in probands and spouses ( P P Msp I site in the promoter region of the apoA-I gene and the Sst I site in the 3′ untranslated region of exon 4 of the apoC-III gene. Haplotypes based on these four variants were constructed and the distributions of haplotype combinations were significantly different ( P Msp I, C317-T; Sst I, C1100-T). The haplotype combinations carrying one of these high risk alleles are associated with elevated lipid levels in probands and in spouses. While these effects can be attributed to the presence of the M2 and S2 minor alleles, these results suggest that the importance of specific allelic haplotypes may be greater than single genotypic effects. —Groenendijk, M., R. M. Cantor, T. W. A. De Bruin, and G. M. Dallinga-Thie. New genetic variants in the apoA-I and apoC-III genes and familial combined hyperlipidemia. J. Lipid Res. 2001. 42: 188–194.
