A Review of Epigenetic Markers of Tobacco and Alcohol Consumption

Abstract

Over the past two decades, advances in genetic technologies have posed unexpected challenges to the ethical and legal framework guiding the application of the most recent advances in healthcare technologies. By and large, these challenges have been successfully met by the introduction by statutes such as the Genetic Information Nondiscrimination Act (GINA). However, over the past several years, these advances in the ability to measure genetic (or heritable) contributions to medical illness have been joined by advances in epigenetic (or acquired) contributions to common medical illnesses. Unfortunately, the moral and legal framework for the use of these epigenetic technologies, which can objectively determine the presence of medical illnesses such as diabetes or the consumption of substances of abuse, is not as well developed. This communication provides an introduction to the fundamentals of epigenetics and then reviews how some of the latest advances in this technology can now be used to assess the consumption of alcohol and tobacco. Next, the possible mechanisms through which these tools could be employed clinically are discussed. Finally, the authors outline the potential for misuse of this technology and suggest that well-informed policy could play a critical role in shaping the optimal implementation of epigenetic technologies.

Figure 1

The heritability of selected common complex medical disorders.

Figure 2

The structure of the serotonin transporter gene (SL6A4 or 5HTT).

Figure 3

The nucleotide sequence of the 799 base pair CpG island that regulates serotonin transporter transcription. The island consists of 83 CpG residues (bold and red) and completely envelops exon 1A (underlined). The six base pair motif indicating a TATA box (indicated by boxed text) is immediately upstream of exon 1A.

Figure 4

A depiction of the relationship of DNA methylation to chromosome condensation. In brief, in response to either internal and external cellular cues, enzymes referred to as DNA methyltransferases (DNMTs) transfer a methyl group from a methyl donor such as folate or methionine to the cytosine residue of a CpG dinucleotide pair. When sufficient numbers of CpG residues in a given area have been methylated and the histone scaffold that is associated with the DNA region has been deacetylated by histone deacetylase (HDAC), the region is condensed into a tightly coiled, transcriptionally inactive chromatin conformation referred to as heterochromatin.

Figure 5

Bisulfite conversion.

Figure 6

Using DNA methylation to determine smoking status.