rs5882
mixedMag 4.5This is a variant in the CETP gene that changes a valine to an isoleucine.
Key Literature Trait Associations
HDL Cholesterol Levels
The G allele reduces CETP activity, leading to higher HDL cholesterol levels. Carriers tend to have a more favorable lipid profile and potentially lower cardiovascular risk. The variant changes isoleucine to valine at position 405.
Longevity
The G (Val/V) allele of rs5882 — particularly in the homozygous G/G (VV) state — is enriched among individuals with exceptional longevity. A landmark JAMA study of 213 Ashkenazi Jewish centenarians (mean age 98.2) found V/V homozygosity 2.9- to 3.6-fold more frequent in long-lived probands and their offspring versus controls, accompanied by lower CETP levels and larger HDL/LDL particles. A 2013 meta-analysis of 8 studies (including 1,021 Han Chinese) showed ethnic heterogeneity: the V allele is protective in Ashkenazi Jewish populations but may be a longevity risk factor in East Asians. The association has not been consistently replicated in broad European populations.
Apolipoprotein B levels
The A (Ile) allele of rs5882 is associated with higher circulating apolipoprotein B levels in large-scale GWAS. In the UK Biobank multi-ancestry GWAS (n=354,097), the A allele showed a beta of +0.023 SD per allele for ApoB (p=9×10⁻²⁰), consistent with the known CETP biology whereby higher CETP activity increases transfer of cholesteryl esters to ApoB-containing particles. This association mirrors the opposing directionality seen for HDL-C at the same locus.
LDL cholesterol
The A (Ile) allele of rs5882 is associated with modestly higher LDL-cholesterol levels. In the UK Biobank GWAS (n=355,197), the A allele showed a beta of +0.017 SD per allele (p=4×10⁻¹¹), consistent with CETP-mediated transfer of cholesteryl esters from HDL to LDL. A pharmacogenomic study (n=252) found that rs5882 carriers on rosuvastatin achieved 13% greater LDL-C reduction compared to non-carriers, suggesting the variant may interact with statin therapy response.
Cognitive function
The G (Val/V) allele, especially the VV homozygous genotype, has been associated with better cognitive preservation in old age. A study of 158 exceptionally long-lived Ashkenazi Jews found VV individuals twice as likely to score above 25 on the MMSE and showed a fivefold enrichment of VV among those with superior memory in a younger cohort, mediated in part by elevated HDL and larger lipoprotein particles. However, a Scottish cohort study (n=525, tested at ages 11 and 79) found no significant association between CETP I405V genotype and cognitive function or lifetime cognitive change, highlighting inconsistent replication outside Ashkenazi Jewish populations.
Total cholesterol
The A (Ile) allele of rs5882 is associated with modestly altered total cholesterol levels in large GWAS. In the UK Biobank (n=355,858 multi-ancestry), the A allele showed a beta of +0.020 SD per allele for total cholesterol (p=2×10⁻¹⁵). The direction of effect reflects the net balance of CETP's actions: while it lowers HDL-C, it also increases ApoB-containing particles, resulting in a net upward shift in total cholesterol.
▶GWAS Catalog Trait Associations (5)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (5)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
High density lipoprotein cholesterol level quantitative trait locus 10; Hyperalphalipoproteinemia 1; not provided; not specified; Coronary artery disorder
View on ClinVar →▶Research that mentions this SNP (2)
▶Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (<emph type="ital">CETP</emph>) Gene With Memory Decline and Incidence of DementiaAssociationN=593Sanders AE et al.(2010)· JAMA
This prospective cohort study of 593 older adults (≥70 years) examined associations between the CETP rs5882 (V405, valine/isoleucine) polymorphism and cognitive decline and dementia risk. Valine homozygotes showed 51% slower episodic memory decline compared to isoleucine homozygotes and had significantly lower risk for incident dementia (HR 0.28, 95% CI 0.10-0.85, P=0.02) and Alzheimer's disease (HR 0.31, 95% CI 0.10-0.95, P=0.03), suggesting a potential protective association of CETP valine homozygosity.
▶Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary RiskMeta-analysisN=195,833Thompson A. et al.(2008)· JAMA
Systematic review of 92 lipid studies (113,833 participants) and 46 coronary disease studies (82,534 participants) examining CETP polymorphisms. TaqIB rs708272 A allele associated with 9.7% decreased CETP mass, 8.6% decreased CETP activity, 4.5% increased HDL-C (95% CI: 3.8%-5.2%), and weakly inverse association with coronary disease (OR 0.95, 95% CI: 0.92-0.99).
Gene information from NCBI Gene. Variant classifications from ClinVar.
Community Wiki
No community notes yet for this variant. Sign in to start one.
Comments
Sign in to join the discussion.
Loading comments…