Rare variants in the lipoprotein lipase (LPL) gene are common in hypertriglyceridemia but rare in Type III hyperlipidemia.

Objective: Genomewide association studies (GWAS) have shown that variation in the lipoprotein lipase gene (LPL) is associated with plasma triglyceride levels but that common variants account for only 1.25% of the variance. The aim of this study was to determine the frequency of rare variants in the LPL gene in patients with various forms of hypertriglyceridemia.

Methods: The DNA sequence of the exons plus exon/intron boundaries of the LPL gene of 313 patients with triglycerides above the 95th percentile for age and sex (107 of whom had triglycerides above 875 mg/dl) and 121 patients with Type III hyperlipidemia was determined.

Results: Twenty rare variants were detected of which seven have been previously reported. All of the rare variants were present as heterozygotes. Sixteen were missense mutations, two were short deletion mutants and there were single nonsense and insertion mutations. Fifteen of the missense mutations resulted in an amino acid change. There were 13 patients (12.1%) with triglycerides above 875 mg/dl and 10 patients (4.9%) with moderately elevated triglycerides, who were carriers of at least one rare, non-synonymous mutation in the LPL gene. Of the patients with Type III HLP, two were carriers of rare variants.

Conclusions: Rare mutations in the LPL gene are frequent in patients with elevated triglycerides.