Common lipid-altering gene variants are associated with therapeutic intervention thresholds of lipid levels in older people

AimsThere are a large number of common genetic variants that have been robustly associated with low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride concentrations. The majority of these have been identified or confirmed in recent genome-wide association studies, but few studies have assessed the combined effect of known lipid variants. We hypothesized that these variants would influence both the need for interventions and myocardial infarction (MI) outcomes. We aimed to estimate combined effects of proven SNPs on LDL, HDL, and triglyceride concentrations and MI history in a representative older population.Methods and resultsIn the InCHIANTI Study of Aging (age ≥65 years), we calculated individual dyslipidaemia risk allele counts for increased LDL (range 4-14, n = 594), reduced HDL (5-16, n = 635), and increased triglycerides (7-16, n = 611). Lipid levels were compared with ATPIII National Cholesterol Education Panel (NCEP) intervention guidelines. Individual variants and the APOE haplotype explained -4), compared with the 21 with 7 or less risk alleles. Similarly, the 35 with 13 or more triglyceride risk alleles were more likely to exceed NCEP intervention thresholds (OR 2.98, 95 CI 1.43-6.22, P = 0.004) compared with the 24 with 10 or less alleles. The number of individuals reporting an MI event was small (n = 67), but an event was more common in the 36 of respondents who had the highest combined risk allele score for all three lipids (OR 3.68, 95 CI 1.21-11.2, P = 0.021) compared with the lowest risk 22.ConclusionIn a representative older population, the cumulative effects of proven LDL- and triglyceride-altering genetic variants increased the odds of crossing the lipid-level threshold for therapeutic intervention by approximately three-fold. All rights reserved.