A loss-of-function CETP variant raises HDL cholesterol without raising ApoA1 or protecting against heart attack in Chinese patients (Nutr Metab Cardiovasc Dis 2021)

Original title: The loss-of-function mutation of CETP affects HDLc levels but not ApoA1 in patients with acute myocardial infarction

Nutr Metab Cardiovasc Dis · 3 November 2020 · 6

Li W, Liu X, Huang C, Liu L, Tan X, Wang X

This study investigated the effects of the East Asian loss-of-function CETP variant rs2303790 (p.D442G) on HDL-cholesterol (HDLc) and ApoA1 levels and its relationship with acute myocardial infarction (AMI), in 2327 AMI patients and 2615 matched controls from the INTERHEART-China study. In controls, both HDLc (1.24 vs 1.04 mmol/L, P=0.001) and ApoA1 (1.48 vs 1.37 mmol/L, P=0.042) were significantly higher in CETP variant G allele carriers than wildtype D allele carriers. In AMI patients, HDLc was significantly higher in variant carriers (1.14 vs 1.01 mmol/L, P=0.013), but ApoA1 did not differ significantly (1.31 vs 1.32 mmol/L, P=0.468). The CETP variant was associated with higher HDLc but not with AMI risk (P=0.564), even after adjustment for multiple cardiovascular risk factors, which the authors suggest may relate to its inability to also raise ApoA1.

Original abstract

Background And Aims: Loss of the cholesteryl ester transfer protein (CETP) function affects HDLc levels, but its effects on major HDL protein component ApoA1 are not well understood in patients with acute myocardial infarction (AMI).

Methods And Results: We investigated the effects of an East Asian loss-of-function variant (rs2303790; p.D442G) in CETP gene on HDLc and ApoA1 levels and its relationship with AMI. A total of 2327 AMI patients and 2615 age- and sex-matched controls from INTERHEART-China study were included. In controls, both levels of HDLc (1.24 vs. 1.04 mmol/L, P = 0.001) and ApoA1 (1.48 vs. 1.37 mmol/L, P = 0.042) were significantly higher in CETP variant G allele carriers compared to CETP wildtype D allele carriers. In AMI patients, levels of HDLc were significantly higher (1.14 vs. 1.01 mmol/L, P = 0.013) while levels of ApoA1 were not statistically difference (1.31 vs. 1.32 mmol/L, P = 0.468) in CETP variant group compared to CETP wildtype group. Moreover, CETP variant is associated with HDLc increase, but is not associated with AMI risk (P = 0.564), even after adjusting for age, sex, history of hypertension and diabetes, waist to hip ratio, smoking, total cholesterol, LDL cholesterol, triglycerides, physical activity, depression, alcohol, vegetables and fruit consumption.

Conclusions: Loss of CETP function is associated with increased HDLc and ApoA1 levels in healthy subjects, and in AMI patients, it is associated with HDLc levels but not ApoA1 levels. The lack of association of CETP variant with AMI may be related to the inability to increase ApoA1 levels and warranted further studies.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.