Genetics
The CETP SNP rs1800775 explains more variance in HDL cholesterol than any other single lipid gene variant studied in older adults (Eur Heart J 2009)
Original title: Common lipid-altering gene variants are associated with therapeutic intervention thresholds of lipid levels in older people
This study in the InCHIANTI Study of Aging (age 65 and older) tested whether common lipid-altering gene variants collectively influence the likelihood of crossing therapeutic intervention thresholds for LDL, HDL, and triglycerides, and myocardial infarction history. Individual dyslipidaemia risk allele counts were calculated for increased LDL (594 participants), reduced HDL (635), and increased triglycerides (611), then compared against National Cholesterol Education Program intervention guidelines. Individual variants and the APOE haplotype each explained less than 2.1% of the variance in their respective lipid concentrations, with the notable exception of the CETP SNP rs1800775, which explained 4.76% of the variance in HDL levels, more than double the next-largest individual effect. Combined risk allele counts outperformed single-SNP effects for LDL (7.1% of variance) and triglycerides (4.8%) but not HDL (3.4%), and the highest-risk quartiles were roughly three-fold more likely to cross intervention thresholds and to report a prior myocardial infarction event.
Original abstract
Aims: There 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 Results: In the InCHIANTI Study of Aging (age >or=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 <2.1% of the variance in their respective lipid concentrations, with the exception of the CETP SNP rs1800775 and HDL levels (4.76%). Combined risk allele counts outperformed the largest single-SNP effects for LDL (explaining 7.1% of variance) and triglycerides (4.8%), but not HDL (3.4%). Risk alleles were divided as near as possible into quartiles. The 31% of respondents with 10 or more LDL increasing alleles were more likely to have LDL levels above the intervention threshold (OR 3.00, 95% CI 1.67-5.39, P = 2.5 x 10(-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%.
Conclusion: In 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.