However, D22S928, mapped within 1Mb of the PPARA gene, was shown to have a modifying effect on plasma apoCIII concentrations (P=0.011) and the combined hyperlipidemic FCHL phenotype (P=0.038).
Linkage and association of the apo AI-CIII-IV gene region to familial combined hyperlipidemia (FCHL) was reported previously, based on the presence of genetic variants in the apo CIII and apo AI gene.
Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia.
A mouse model displaying some of the features of FCHL was created by crossing mice carrying the human apolipoprotein C-III (APOC3) transgene with mice deficient in the LDL receptor.
It is considerable clinical relevance that the apoC-III gene may be acting as a modifier gene that is only expressed in the presence of other factors (e.g., increased VLDL flux, low LPL activity) and therefore may predispose those members of FCHL families carrying the T1100 allele to express the FCHL phenotype.
By using chemical cleavage mismatch analysis and the single strand conformation polymorphism technique, DNA fragments of the apo CIII gene, including the 5' flanking region and all the exons, were screened for sequence changes underlying the observed association between familial combined hyperlipidaemia (FCHL) and the apo AI-CIII-AIV gene cluster in affected individuals from eight FCHL families.