Resequencing the apolipoprotein A5 (APOA5) gene in patients with various forms of hypertriglyceridemia.

Objective: Genomewide association studies (GWAS), conventional association studies and the characterization of families with ApoA5 deficiency have shown that variation in the apolipoprotein A5 (APOA5) gene is associated with plasma triglyceride levels. The aim of this study was to determine the frequency of rare variants in the APOA5 gene in patients with various forms of hypertriglyceridemia.

Methods: The DNA sequence of the exons plus exon/intron boundaries of the APOA5 gene of 291 patients with triglycerides above the 95th percentile for age and sex (98 of whom had triglycerides above 875 mg/dl), 111 patients with APOE2/2 genotype of whom 100 had Type III Hyperlipidemia and 108 probands with triglycerides below the 25th percentile for age and sex was determined.

Results: Twenty four variants were detected of which eight have been previously reported. There were nine patients with triglycerides above 875 mg/dl and nine patients with moderately elevated triglycerides who were carriers of at least one deleterious mutation in the APOA5 gene. Of the patients with Type III HLP, three (3%) were carriers of rare variants and there was a single rare variant detected in the group of probands with triglycerides below the 25th percentile for age and sex.

Conclusions: Rare mutations in the APOA5 gene are more frequent in patients with elevated triglycerides than in those with Type III HLP.