Abstract 3195: The APOA5 Gene is Associated with Familial Combined Hyperlipidemia and Dyslipidemia
Objective: The apolipoprotein A5 gene (APOA5) is one of the most recently identified gene in the apolipoprotein APOA1-C3-A4-A5 cluster and is associated with plasma triglyceride (TG) and HDL-cholesterol (HDL-c) levels. The APOA5 gene resides on chromosome 11, where linkage analyses have identified a locus for familial combined hyperlipidemia (FCH), the most common genetic lipid disorder. The aim of the present study was to investigate whether the APOA5 gene is associated with FCH and its related phenotypes.
Methods: The study population included 36 families, compromising 620 individuals, of whom 158 individuals were diagnosed as FCH patient. The diagnosis of FCH was based on plasma TG, total cholesterol (TC) and apolipoprotein B (apoB) levels, using the recently published nomogram. Two polymorphisms in the APOA5 gene (−1131T>C and S19W) were genotyped with PCR-RFLP. The FBAT program was used for the analysis of each polymorphism and haplotype.
Results: Haplotype analysis showed that APOA5 was associated with FCH (p=0.03). Associations were also found with individual lipid and lipoprotein levels for the APOA5 haplotypes (TC (p=0.03), TG (p<0.01), apoB (p=.01), HDL-c (p=.02), small dense LDL (p=.01), VLDL-c (p<.01) and VLDL-tg levels (p<.01)). Furthermore, FCH patients carrying a -1131C allele or a 19W allele had higher TG (+5% and +7%), VLDL-c (+7% and +5%) and VLDL-tg levels (+4% and +3%), compared to wildtype homozygotes.
Conclusion: In these Dutch FCH families, the APOA5 gene is associated with FCH and dyslipidemia. APOA5 might be the gene underlying the linkage signal previously detected on chromosome 11 for FCH.