Alcohol and Heart Disease: it’s in Your Genes

by Patricia Shelton, MD

For heart disease, popular belief can be misleading

Many people have been happy to find out that alcohol may protect against heart disease. In studies, moderate consumption of alcohol (one drink per day for women, or two drinks per day for men) has been associated with a lower risk of heart disease, compared to no alcohol consumption. (Rates of many diseases rise sharply with higher levels of alcohol consumption, so some is good, but more is not necessarily better.) How often do you get health advice that’s also fun and indulgent? After learning about this association, many people begin drinking the recommended glass or two of wine every night. (Just for the record, you can’t save them up; seven drinks once a week is not the same as one drink every night.)

However, the link between moderate alcohol consumption and reduced risk of heart disease shows up when analyzing a whole population. Yet none of us is average in every way; the analysis of a large group obscures potentially important differences between individuals in that group. As technology develops and makes DNA analysis easier and cheaper, scientists are increasingly seeking to individualize health advice based on genetic differences.

Unfortunately, the link between alcohol and heart disease may only exist in a group of people with a certain genetic variation. If you’re not part of that group, moderate alcohol consumption may not protect your heart after all.

 

HDL, LDL, CETP, etc.

To understand the gene we’re looking at, let’s first get some background in the science of coronary heart disease risk. Many people are familiar with cholesterol, and with the idea that “high cholesterol” is linked to heart attacks. Cholesterol is a fatty substance that’s necessary in the body, both as a component of cell membranes and as a precursor for hormones; however, in excess and under certain conditions, it can deposit into the walls of arteries, narrowing and hardening them. Cholesterol is carried in the blood by various proteins, called lipoproteins. Some of these, the low-density lipoproteins (LDLs), carry cholesterol through the blood to the body’s tissues; others, the high-density lipoproteins (HDLs), carry excess cholesterol from the rest of the body to the liver, where it will be stored or processed. Because LDL carries more cholesterol into the blood while HDL causes it to be removed, higher levels of LDL in the blood have been associated with a greater risk of heart disease, while higher levels of HDL are cardioprotective (meaning that they reduce the risk of heart disease). When you receive a “cholesterol test,” the various levels of LDL and HDL are measured. Alcohol raises HDL levels, which may be one of the main ways it reduces the risk of heart disease.

Cholesteryl ester transfer protein, or CETP, is less well-known than LDL and HDL, but is an integral part of the same pathway. CETP transfers cholesterol between these various lipoproteins, and it’s known to have a link to heart disease. Inhibitors of CETP activity are under development as potential pharmacological agents to lower the risk of heart disease (though they aren’t yet out of the research stage, and the results have been somewhat disappointing), and genetic variations in CETP have been observed to be correlated with heart disease.

 

Genetic Variations in CETP

A genetic variation in CETP that’s been implicated in heart disease is the CETP Taq1B polymorphism. (A polymorphism is a gene in which there are two or more forms existing in the population.) The two types (or alleles) are called B1 and B2; each person has two copies of each gene (one from each parent), so an individual’s genotype (their set of alleles) can be B1B1, B1B2, or B2B2. The B2 allele has been associated with higher HDL levels in the blood (i.e., a lower risk of heart disease); those who are B2B2 generally have the highest HDL.

A group of researchers in Sweden sought to find out whether a person’s CETP Taq1B status would modify the cardioprotective effect of alcohol. (Taq1B has been associated with HDL levels, and the cardioprotective effect of alcohol may be mediated through HDL, so it made sense to ask whether Taq1B and this effect of alcohol are associated.) They used a huge genetic database that was collected in Sweden in 2001, and compared that healthy population to a group of people with heart disease, whose blood was tested to determine which CETP Taq1B alleles they were carrying. They found that, as expected, intermediate alcohol consumption lowered the risk of heart disease. They also found that this effect was modified by CETP Taq1B status. Those who were B2B2 had the strongest effect of alcohol, while the effect was much weaker for people with at least one copy of B1 in their genes. (Interestingly, this only reached statistical significance in men, but the researchers state that it’s likely that happened because the number of women in the sample was too small. A larger study of women would be helpful, to be sure that this applies to both genders.)

 

What Does This Mean For You?

Those whose genotype is B2B2 may have multiple reasons to believe they’re fortunate, at least when it comes to the risk of heart disease. It’s likely that they have higher HDL, and alcohol is available to them as a cardioprotective agent.

If you don’t know your CETP Taq1B status, you might want to learn about it before you invest in a drink or two of alcohol each night. However, there isn’t a commercially-available test for CETP Taq1B, because the research on this gene is still too new. Because this might make it difficult to find out which alleles you carry, you’ll have to choose based on your medical and family history and your own preferences whether you want to give alcohol’s potential cardioprotective effect a try.