The Genetics of IPF

This page was completed by Kelly Griffith

Features of Idiopathic Pulmonary Fibrosis (IPF)

Let's start by breaking down what that means:

Idiopathic = unknown cause/reason
Pulmonary = in the lungs
Fibrosis = formation of scars

Altogether, IPF is the scarring of the lungs from unknown causes.

Usually first presents as shortness of breath, coughing and/or fatigue (tiredness).
This disease is progressive and typically worsens with time.
This is a rare disease (about 3 cases per 1000 people).

Image (at left) from Physiopedia.com

What do you mean by "genetics"?

All living things are made up of cells and cells have DNA in them. This DNA plays a part in how our bodies function and what we look like, such as in the case of eye color or height. The specific letters in our DNA, called nucleotides, determine how our DNA is read. Many nucleotides combine to make a whole gene, which provides instructions for coding for a trait or a function. If one or more of these letters changes, then the way it is read changes. This means the trait or the function could also change.

We call these changes mutations, variants, alterations, anomalies, or other similar words. Changes can occur for any number of reasons, but if our parents or children have these same changes, they are called hereditary changes because they have been passed down between generations.

Our DNA is coiled up and compacted into a chromosome. The very ends of the chromosome are called telomeres (telo- meaning distant, or far away). IPF can be due to changes in individual genes, multiple genes, or even genes specifically located on the telomeres.

Image credit: Yougenome.org

Many genes are connected to pulmonary fibrosis

Some IPF Genes are on the Telomeres

Telomeres (the far tips of chromosomes) shorten with age. When they shorten, we sometimes lose important parts of our DNA. When telomeres are lost, it means that tissue (like skin, for example) can't be replaced properly. In the case of IPF, a loss of the telomeres means that the lungs won't heal as well as they used to. When this happens often enough and for long enough, scarring inside the lungs can occur, and this can lead to IPF.

Image Credit (left) Earthsky.org

Some IPF Genes Cause changes to the Mucous in our Lungs

Our bodies create something called a surfactant. A surfactant is basically a slippery liquid that acts as a lubricant, much like oil acts as a lubricant in the engine of a car. Where oil keeps the engine from seizing, surfactant keeps our lungs from seizing. If a gene that codes for surfactant changes, then this surfactant doesn't work the way it should. In cases where we don't have enough surfactant, our lungs can't expand and contract easily, making it hard to breath. If we have too much surfactant, it floods our lungs, causing infections and difficulty breathing. Both cases can cause our lungs to scar.

Image Credit (above) ResearchGate.net

The image above shows an example of CT scan of lungs that have too much mucous and are affected by pulmonary fibrosis. The lungs are the two bean-shaped dark sections of the pictures. Normally, lungs don't have all the white spots that are dotting this picture.

Image Credit NEJM.org

MUC5B - the most common genetic cause

There is a common mutation seen in the MUC5B gene that is linked to pulmonary fibrosis. The MUC5B gene codes for one of five kinds of mucous that our body makes. Much like the surfactant genes listed above, MUC5B helps to lubricate. A change in the MUC5B gene can happen with even one change to one letter in our DNA for that gene. Even just that one letter change is enough to cause difficulties for the person it affects. However, this one gene won't cause IPF all on its own. For a change in the MUC5B gene to have an impact, it has to be paired with changes to other genes in the DNA, too, making it polygenic (poly- meaning "many", genic- meaning "genes"). This means that other genes have to have changes or mutations, too, otherwise a person won't have IPF as a result of the change.

It's thought that the impacts of a person's environment can also change this MUC5B gene. For example, being around a lot of second-hand smoke might affect this.

The Future and Genetic Testing

Can I get tested?

Most often, genetic testing for IPF is limited. Because there are a lot of genes that contribute to IPF, it makes the testing difficult. People who have a family history of IPF, or people who already know their family has a genetic variant are more likely to be able to get genetic testing. Testing for just the MUC5B gene is easier than testing for all the possible genes that contribute to IPF and may be more available.

If you're curious about testing, discuss the options with your doctor, pulmonologist, geneticist, or genetic counselor. Genetics is always advancing, so remember that as we learn more about genetics and IPF, there may be more options in the future.

Image Credit ArielMedicine.com

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