Introduction: Familial dysbetalipoproteinemia (FD) is an autosomal recessive (rarely dominant) inherited disorder that is almost exclusively associated with the apolipoprotein E gene (APOE).However, only a small proportion of patients with the typical APOE2/E2 genotype develop phenotype - the mixed dyslipidemia (DLP) - in the context of other metabolic or as yet undescribed genetic factors.
Methods: We screened 71 FD patients and 90 controls (all APOE2/E2 homozygotes, according the rs429358) for 18 single nucleotide polymorphisms (SNPs) in genes involved in triglyceride metabolism.
Results: Two SNPs were significantly associated with the FD phenotype (rs439401 within APOE and rs964184 within APOA5). An unweighted gene risk score (GRS; sum of risk alleles) was analysed as a genetic predictor of FD development in patients with the APOE2/E2 baseline genotype. The unweighted GRS constructed from the 5 strongest SNPs (within the APOE, APOA5, CFT1, LPL, and TYW1B genes) reliably discriminated between FD and controls (OR 4.97; CI (2.24-11.06), P < 0.00003).
Conclusions: Several SNPs, i.e., individual additive genetic factors, were found to influence the development of FD. Thus, unweighted GRS clearly improves the prediction of FD development in APOE2/E2 homozygotes.