This is a beginning of a series of blogs that explores the emerging view regarding the genetic risk of kidney disease. Consider this series your crash course in epigenetics! We will also discuss epigenetics in kidney disease. But before we dive in, let’s start with a refresher on genetics.
By Lara Zakaria, PharmD CNS CDN IFMCP
You may remember from your high school science class that DNA is a long and windy spiral made up of millions of nucleotides. There are 4 nucleotide bases (adenine, cytosine, guanine, thymine), the sequence of which determines how genetic traits are expressed.
The nucleotide sequence is the foundation of about 20,000 genes. Our cells read the genetic sequence and use it to make thousands of proteins that are essential for carrying out biological functions that maintain life.
Alterations in the sequence, like single nucleotide polymorphisms (SNPs), or errors in the code, affect the efficiency of the protein production process. These may sometimes lead to disease or increased risk for disease. Interestingly, on occasion, they may have no effect on risk and may even be protective against disease.
Genetics and disease risk, the old view
For decades, scientists assumed that if we were to interpret the DNA sequence, we’d be able to “crack the code” and unlock the potential to identify and repair “broken code” and prevent or reverse disease. This was an exciting prospect; however, as it turns out, there’s actually another way.
Since the early 2000’s researchers began to notice that people with so-called “bad genes” weren’t expressing disease the way we would have predicted, and a new theory began to shape the paradigm of genetics. What if lifestyle, environmental influences, and emotional factors played a role in genetic expression? This was the beginning of the emergence of a new field of research called epigenetics.
What is Epigenetics?: The “protein factory”
If epigenetics had a tagline, it would be: Your genes are not your destiny.
Recall that the nucleotide sequence of DNA codes for the production of proteins that are used for thousands of biological processes in the body. So, we’ll call this the “protein factory.” Now, imagine that your DNA acts like a conveyer belt and that there’s a scanner that reads the DNA sequence, interpreting the instructions for protein production.
Now, let’s imagine there’s a factory worker that sits at a switchboard. He’s in charge of a lever that controls the speed of the “conveyer belt” and a button that can turn the scanner on or off. Our factory worker can speed up the belt to produce proteins faster or turn it down to make less. He can also decide to turn off the “scanner,” so it skips certain genes and doesn’t make that particular protein (maybe there’s already or much of it, and we don’t need more).
Though it’s a rough example, this is essentially how epigenetics influence genetic expression, protein production, and in turn, whether a genetic risk is expressed (leading to disease) or suppressed (not getting the disease). In other words, in our example, factors that influence disease risk are “the boss,” who instructs our “protein factory” worker on how to operate the lever and scanner.
That’s why we summarize this evolved understanding of genetics to say, “Our genes are not our destiny.” We now understand that they are not set in stone at birth, determining our fate. Our lifestyle and environment (the boss) help to shape how your epigenetics (the factory worker at the switchboard) expresses your health outcomes.
Here’s a key takeaway: Just as much as good lifestyle habits can reduce disease risk by turning off problematic genes, our poor decisions can increase our disease risk.
How epigenetics changes the conversation about disease risk?
You can probably start to see how these revelations about the role of lifestyle and environment have completely changed the conversation about the genetic risk of disease. Scientists who once thought that we have to literally change our genes to modify disease risk are now exploring how to use epigenetic influence to improve health outcomes.
Lifestyle factors like diet, sleep, meditation, and exercise are things we have control over and have a tremendous influence on genetic expression. Limiting exposure to environmental toxins (like food additives, pesticides, heavy metals, and plastics) and supporting the body’s natural detoxification pathways is another essential aspect to keep in mind.
Ever wonder how relatives that haven’t met or spent little time together may express similar personality traits or likes and dislikes?
Well, epigenetics may even play a role in the expression of traits like personality, stress resilience, and even likes and dislikes (like food!). As it turns out, the experience of past trauma may also be passed down as a result of epigenetics.
So, think of ancestors who survived famine, war, or torture – we now realize their experiences can influence genetic expression. There’s even evidence that experience during pregnancy can influence a baby’s risk later in life epigenetically.
Could this be part of the reason why certain populations are more prone to certain chronic diseases? Future research may tell us more.
The role of epigenetics in kidney disease
The field of epigenetics is still in its early phases, and the publications exploring the relationship to kidney disease specifically are even younger. However, there’s an exciting and growing body of research exploring these ties.
Furthermore, the breakthroughs in the fields of cancer and aging are very encouraging and give us insight into what might be successful for kidney disease. As we learn more, this emerging research may help us to slow disease progression and potentially even reverse kidney disease in the near future.
References
- Weinhold, B. Epigenetics: the science of change. Environ Health Perspect. 2006;114(3):A160-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1392256/
- Mazzio EA, Soliman KF. Basic concepts of epigenetics: impact of environmental signals on gene expression. Epigenetics. 2012;7(2):119-30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335905/
- Tammen SA, Friso S, Choi SW. Epigenetics: the link between nature and nurture. Mol Aspects Med. 2012;34(4):753-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515707/
- Dwivedi, Rama S. et al. Beyond genetics: epigenetic code in chronic kidney disease. Kidney International, 2011; 79(1): 23 – 32 https://www.kidney-international.org/article/S0085-2538(15)54674-7/fulltext
- Wanner N, Bechtel-Walz W. Epigenetics of kidney disease. Cell Tissue Res. 2017 Jul;369(1):75-92. Epub 2017 Mar 13. https://www.ncbi.nlm.nih.gov/pubmed/28286899
