# CETP I405V variant

CETP (cholesteryl ester transfer protein) swaps cholesteryl esters out of HDL for triglycerides from VLDL and LDL, which effectively lowers your HDL cholesterol. The I405V variant (rs5882) in the CETP gene reduces CETP activity. It is enriched in Ashkenazi Jewish centenarians and their children, versus controls, in the Longevity Genes Project at Albert Einstein College of Medicine (Barzilai et al., 2003). It comes with unusually high HDL and large HDL particles. Large HDL particles are better at reverse cholesterol transport, and are linked to lower heart and cognitive disease risk. The variant is a useful lesson: a natural loss-of-function gene can mimic the heart benefit that drug-makers chased with CETP inhibitors. Several of those drugs failed in trials despite raising HDL, which suggests the quality of HDL particles matters more than the quantity.

## Sources

- Barzilai N, Atzmon G, Schechter C, et al.. (2003). Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA. https://doi.org/10.1001/jama.290.15.2030

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_Canonical: https://longevity-switzerland.com/en/glossary/cetp-i405v · Part of Longevity Cities · Updated 2026-06-22_