Physicians have long been perplexed by this disease we call asthma. What’s the root cause? Why do some have it worse than others? Ongoing research in the field of genetics is leading researchers closer and closer to the answers. That said, here is what is presently known about genetics and asthma.
DNA: The various tissues of our bodies are made up of 50 trillion cells, and each one has a long, spiraling DNA (deoxyribonucleic acid) sequence, each of which is organized into short segments called genes. DNA is tightly wound and organized into chromosomes. Every human cell has 23 pairs of chromosomes (base pairs). Among the base pairs, one strand of DNA comes from your mom and the other from your dad. 1, 2
Genes: Each gene contains a recipe (code, blueprint or set of rules) for creating 1-10 proteins that tell cells what to do. In our case, be an airway cell, be an alveolar cell, or be an immune cell called a T-helper cell. There are an estimated 300,000 proteins inside your body, and they each play a unique role in making you and keeping you healthy. 1, 2, 12
Human Genome: During the mid 1980s, efforts were initiated to map out (sequence) the entire human genome. By 1990, the Human Genome Project began with the goal of sequencing the human genome within 15 years. By 2003, they had sequenced 99% of the human genome. They were surprised to learn each person has only 30,000 genes. 3
So, with the genome complete, the goal shifted to learning the various genetic recipes, and how the various parts work together to make a healthy or unhealthy person.
Gene Mutations: Most genes are the same from one person to the next. However, a small percentage (about 0.4%) are unique due to changes in the recipe that occurred during cell division. 4 When a cell changes it is called a gene mutation or variation. Mutations are normal, and they determine the characteristics that make us unique. For instance, we all have genes for making eyes, but variations on these genes determine unique eye characteristics, such as whether you have brown, blue or green eyes. 2, 4
Asthma Genes. These are gene mutations that tell cells to do something abnormal and that contribute to the development of inflammatory diseases like allergies and asthma. The first asthma gene was discovered in 1989, and since then over 100 have been discovered. The quest to understand the role each asthma gene plays in the development of asthma is ongoing. 5
Genotype: This is the combination of genes and gene mutations (including asthma genes) handed down from parent to child. Since asthma genes are considered to be part of a person’s genotype, it can probably be considered hereditary. 5, 9
Gene Expression: How genes and gene mutations express themselves determine the characteristics that make each of us unique. It determines skin color, hair color, eye color, and even personality. They also determine how your asthma will express itself. 9
Asthma Gene Expression: Some diseases (like cystic fibrosis) are caused by one gene mutation. However, researchers believe asthma is caused by many gene mutations randomly scattered along your genome or genotype. Each of these asthma genes expresses itself in a unique way, the combination of which determines the characteristics of your asthma. 6 In this way, genes determine what triggers your asthma, what your symptoms will be, how severe your asthma will be, and what medicines will work or will not work. This may also explain why some have it worse than others.
Inactive -vs- Active: Some asthma genes cause asthma no matter what you do or where you live. Other asthma genes are inactive and only become active due to some sort of environmental exposure, such as exposure to certain foods, stress, air pollution, tobacco smoke, respiratory infections, or allergens. 11 This may explain why some develop asthma in childhood, while others develop it later in life.
Heterogenous. The fact that each person has a different combination of asthma genes probably explains why the asthma presentation is unique from one asthmatic to the next. This may also explain the complexity of this disease, and why the root cause continues to elude researchers. Basically, researchers have learned asthma is a single disease that has many different root causes, and this has lead to the creation of phenotypes. 6
Phenotypes: Since asthma is so complex, researchers have found it helpful to divide the disease into different phenotypes. These are observable characteristics that result from how your asthma genes express themselves in response to asthma triggers. The goal is to learn what specific genes work together to cause each phenotype in response to environmental exposure. 9 Researchers have further simplified this by creating various asthma subgroups.
Subgroups. A better understanding of asthma phenotypes has lead researchers to dividing asthma into various subgroups or subtyes, such as allergic asthma, non-allergic asthma, obese asthma, premenopausal asthma, exercise induced asthma, asthma/COPD overlap syndrome, etc. Essentially, these are all different types of asthma. While some may respond well to traditional asthma medicines, others may require unique treatment options to obtain ideal asthma control. So, the goal here is to identify all the various asthma subgroups and come up with asthma guidelines catered specifically for each one.
The future looks bright! Genetic research is an evolving field in science, and researchers are just beginning to understand how asthma genes work together to cause asthma.
It actually appears that there are many root causes of asthma (or many genetic root causes). The quest is ongoing to learn what each specific asthma gene does, how they work together in response to environmental triggers to cause asthma, and methods of blocking their effects. This should give pharmaceutical companies the “building blocks” they need to develop medicines catered to each specific phenotype and subtype, thereby giving each physician better options for helping each individual asthmatic. 8
The accumulation of information learned through genetic research shows how complex this disease is. However, the hope is that it will be only a matter of time before researchers make that revolutionary breakthrough that leads them to the true root causes of our disease, along with better treatment options catered specifically for you.