Alcohol consumption, TaqIB polymorphism of cholesteryl ester transfer protein, high-density lipoprotein cholesterol, and risk of coronary heart disease in men and women

M K Jensen,K J Mukamal,K Overvad,E B Rimm

doi:10.1093/eurheartj/ehm517

M K Jensen, K J Mukamal + Show 2 more

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https://doi.org/10.1093/eurheartj/ehm517

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Abstract

To investigate whether a common polymorphism in the cholesteryl ester transfer protein (CETP) gene modifies the relationship of alcohol intake with high-density lipoprotein cholesterol (HDL-C) and risk of coronary heart disease (CHD). Parallel nested case-control studies among women [Nurses' Health Study (NHS)] and men [Health Professionals Follow-up Study (HPFS)] where 246 women and 259 men who developed incident CHD were matched to controls (1:2) on age and smoking. The TaqIB variant and alcohol consumption were associated with higher HDL-C, with the most pronounced effects of alcohol among B2 carriers. In the NHS we did not find an inverse association between alcohol and CHD in B2 non-carriers (P trend: 0.5), but did among B2 carriers (P trend <0.01). Among non-carriers the odds ratio (OR) for CHD among women with an intake of 5-14 g/day was 1.4 (95% CI: 0.6-3.7) compared with non-drinkers, whereas among B2 carriers the OR was 0.4 (0.2-0.8). Results in men were less suggestive of an interaction; corresponding OR's were 1.9 (0.8-4.5) and 0.9 (0.5-1.6), for B2 non-carriers and carriers, respectively. The association of alcohol with HDL-C levels was modified by CETP TaqIB2 carrier status, and there was also a suggestion of a gene-environment interaction on the risk of CHD.

Highlights

In prospective cohort studies, moderate alcohol consumption is associated with a lower risk of coronary heart disease (CHD) than abstention or very light drinking.[1,2] The primary mechanism proposed for this association is the higher levels of high-density lipoprotein cholesterol (HDL-C) found among moderate drinkers.[3]
One pathway could be through regulation of cholesteryl ester transfer protein (CETP) activity, as CETP mediates transfer of cholesteryl esters from HDL to low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) particles
We have previously reported on the association between alcohol consumption and risk of CHD in these nested case-control studies,[7] which was similar to the relationship found in the full Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts.[17,22]

Summary

Introduction

Moderate alcohol consumption is associated with a lower risk of coronary heart disease (CHD) than abstention or very light drinking.[1,2] The primary mechanism proposed for this association is the higher levels of high-density lipoprotein cholesterol (HDL-C) found among moderate drinkers.[3]. Biological mechanisms underlying the positive association between alcohol and HDL-C are not yet fully understood. One pathway could be through regulation of cholesteryl ester transfer protein (CETP) activity, as CETP mediates transfer of cholesteryl esters from HDL to low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) particles. The concentration of CETP is inversely associated with HDL-C levels.[8,9] Observational studies have reported lower CETP activity among both alcohol abusers and young men with moderate alcohol

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