APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia.

BACKGROUND

Several known candidate gene variants are useful markers for diagnosing hyperlipoproteinemia. In an attempt to identify other useful variants, we evaluated the association of two common APOA5 single-nucleotide polymorphisms across the range of classic hyperlipoproteinemia phenotypes.

METHODS

We assessed plasma lipoprotein profiles and APOA5 S19W and -1131T>C genotypes in 678 adults from a single tertiary referral lipid clinic and in 373 normolipidemic controls matched for age and sex, all of European ancestry.

RESULTS

We observed significant stepwise relationships between APOA5 minor allele carrier frequencies and plasma triglyceride quartiles. The odds ratios for hyperlipoproteinemia types 2B, 3, 4 and 5 in APOA5 S19W carriers were 3.11 (95% CI 1.63-5.95), 4.76 (2.25-10.1), 2.89 (1.17-7.18) and 6.16 (3.66-10.3), respectively. For APOA5 -1131T>C carriers, the odds ratios for these hyperlipoproteinemia subtypes were 2.23 (95% CI 1.21-4.08), 3.18 (1.55-6.52), 3.95 (1.85-8.45) and 4.24 (2.64-6.81), respectively. The overall odds ratio for the presence of either allele in lipid clinic patients was 2.58 (95% CI 1.89-3.52).

CONCLUSIONS

A high proportion of patients with four classic hyperlipoproteinemia phenotypes are carriers of either the APOA5 S19W or -1131T>C variant or both. These two variants are robust genetic biomarkers of a range of clinical hyperlipoproteinemia phenotypes linked by hypertriglyceridemia.