The following is a summary of “Genome‐Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the CETP Gene,” published in the November 2023 issue of Cardiology by Yu et al.

Atherosclerotic cardiovascular disease (ASCVD) risk elevates significantly with age, yet certain older individuals remain unaffected despite high predicted risk. This study aims to investigate potential cardioprotective genetic variants contributing to ASCVD resilience in asymptomatic older individuals without prevalent ASCVD.

Utilizing a genome-wide association study in asymptomatic individuals aged ≥70 years without prior ASCVD events (N=12,031) from the ASPREE trial, we identified two independent variants, rs9939224 (P<5×10^-8) and rs56156922 (P<10^-6), within the CETP gene. CETP regulates plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) levels and is a therapeutic target. Validation in the UK Biobank (N=13,888 individuals aged ≥69 years without prevalent ASCVD) confirmed the associations. Carriers of these CETP variants exhibited elevated plasma high-density lipoprotein cholesterol levels, decreased plasma low-density lipoprotein cholesterol levels, and reduced incident ASCVD risk during follow-up. Expression quantitative trait loci analysis suggested that these CETP variants might suppress CETP gene expression across various tissues. Moreover, among ASPREE trial participants with retinal imaging and genetic data (N=3,917), no association was observed between genetic CETP inhibition and an increased risk of age-related macular degeneration.

Their study underscores the association of common genetic variants within the CETP gene region with cardiovascular resilience during aging in asymptomatic individuals, shedding light on potential protective mechanisms against ASCVD.

Source: ahajournals.org/doi/10.1161/JAHA.123.031459