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Heart benefits of alcohol may not apply to everyone

CETP TaqiB genotype modifies the association between alcohol and coronary heart disease: The INTERGENE case-control study.

Study under review: CETP TaqIB genotype modifies the association between alcohol and coronary heart disease: The INTERGENE case-control study

Introduction

With advice coming from everyone from physicians to bartenders, a common message broadcast during the past couple decades has been that moderate consumption of alcohol is not just allowable, but beneficial for heart disease. Indeed, imbibing to the tune of one drink daily for women, or two drinks daily for men, has been associated with lower risk of cardiovascular disease.

Proposed mechanisms for the protective effect of alcohol on coronary heart disease (CHD) include the potential benefits from the antioxidant effects of polyphenols in wine, and an increase in high density lipoprotein (HDL) levels. HDL’s most well known function is to transport cholesterol from arteries throughout the body back to the liver, preventing cholesterol from being deposited in the arteries, which would cause blockages.

Lipid-containing particles in the blood often gain and lose different types of lipids, such as cholesterol and triglycerides. The ability of HDL to transfer cholesterol into particles like VLDL is partially regulated by cholesteryl ester transfer protein (CETP). CETP promotes transfer of HDL cholesterol into VLDL, and in exchange HDL receives triglycerides. CETP is hence thought to reduce HDL cholesterol, so less CETP in your blood means HDL particles would balloon up with more cholesterol, and more CETP would mean HDL particles would carry less cholesterol.

Hold on, less HDL cholesterol … isn’t that a bad thing? Not necessarily, as HDL is more complex than just the “good cholesterol” moniker it has taken on in public parlance (and unfortunately physician office parlance as well). HDL also has a lesser known, but important role in the immune system[1], performing a variety of functions, such as binding toxic substances in the blood. HDL can be anti-inflammatory or inflammatory[2], depending on the disease state of the body. HDL and LDL are markers of disease, but they each have physiological functions important to the body, and neither are absolute determiners of or protectors against heart disease.

Back to CETP. There is a known polymorphism in the gene that encodes CETP called CETP TaqIB. A polymorphism is when a particular gene has two or more relatively common possible nucleotide sequences at a given site in the DNA. Both versions of the DNA sequence would be considered "normal," with neither likely to directly cause debilitating disease, like a rare mutation might. However different polymorphisms may still influence susceptibility to disease.

This study looked at how two polymorphisms in the CETP gene affect the odds of having CHD at varying levels of alcohol intake. The two different alleles (gene variants) of CETP are called B1 and B2. B2 is associated with decreased CETP mass and increased HDL cholesterol. Given that we have two copies each of gene, the three different genotype options in a given subject are B1B1, B1B2, or B2B2.

A previous study[3] showed that men with B2B2 genotype who have an ethanol intake of 50 g (about three drinks) or more per day had about a 60% lower risk of heart attacks than men with lower or no alcohol intake. This protective effect of larger amounts of alcohol was not seen in people with the B1B1 or B1B2 genotypes. On the other hand, in a study in a Mediterranean cohort[4], no interaction between CETP TaqIB, alcohol intake, and CHD was observed.

Why is that? One reason could be simply different populations. As seen in Figure 1, different populations can have substantially different CETP genotype frequencies. Rodents such as mice have no CETP gene, and also have lower risk of atherosclerosis, though many other factors may be responsible this. Complete CETP deficiency is rare mutation in humans, although it’s much more frequent in one area of northern Japan[5]. While the frequency of this mutation is higher in those with heart disease, at least in that area of Japan, recent studies have shown that the extremely cholesterol-rich HDL in these people still maintains it’s antioxidative function[6] and ability to move cholesterol[7] out of areas of cholesterol buildup. So the impact of CETP on heart disease is still very much up in the air.

Figure 1: CETP B2B2 allele frequency in different populations

The aim of the current study was to re-examine the effect of alcohol intake and its interaction with CETP Taq1B polymorphism on CHD odds.

Moderate alcohol intake is often encouraged to help ward off heart disease. This advice is largely based on HDL effects, but these effects may also be modified by your genotype.

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Other Articles in Issue #03 (January 2015)