ApoA5 genetic variants as robust genetic biomarkers of various clinical hyperlipoproteinaemia phenotypes linked by hypertriglyceridaemia
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Several known gene variants are useful markers for the diagnosis of hyperlipoproteinaemia, and may be of use in predicting susceptibility to hypertriglyceridaemia or identify responders to interventions aimed at lowering plasma triglycerides. The association of two common APOA5 single-nucleotide polymorphisms was evaluated across the range of classic hyperlipoproteinaemia phenotypes in an effort to identify other useful variants. To this end, plasma lipoprotein profiles and APOA5 S19W and -1131T>C genotypes were assessed in 678 adults from a tertiary referral lipid clinic and in 373 age- and sex-matched controls (all of European ancestry). There were significant stepwise relationships between APOA5 minor allele carrier frequencies and plasma triglyceride quartiles. For APOA5 S19W carriers, the odds ratio was 3.11 for hyperlipoproteinaemia type 2B, 4.76 for type 3, 2.89 for type 4, and 6.16 for type 5. In APOA5 -1131T>C carriers, the odds ratio was 2.23 for hyperlipoproteinaemia type 2B, 3.18 for type 3, 3.95 for type 4, and 4.24 for type 5. In patients from the lipid clinic, the overall odds ratio for the presence of either allele was 2.58. In conclusion, a high proportion of patients with four classic hyperlipoproteinaemia phenotypes are carriers of either the APOA5 S19W or -1131T>C variant or both. These two variants appear to be robust markers for a range of clinical hyperlipoproteinaemia phenotypes previously considered as distinct and disparate, but which all share a hypertriglyceridaemia phenotype.
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