The causes of hidradenitis suppurativa (HS) are not fully understood, but researchers believe there is a genetic component to the condition. Diseases that are genetic are associated with variations in DNA sequence. These genetic variants, also called genetic mutations, can be inherited from a person’s biological parents or can occur during the course of life, unrelated to heredity.
To understand more about the genetics of hidradenitis suppurativa, myHSteam spoke with Dr. Lynn Petukhova, a genetic epidemiologist in the department of epidemiology at Columbia University in New York. Dr. Petukhova’s research investigates follicular (hair follicle) diseases that occur when communication with the immune system goes awry. HS is a condition she is particularly interested in.
“My ultimate goal is to understand biology because that will give us a direct road forward to improving how HS symptoms are managed,” said Dr. Petukhova, who studies factors that increase susceptibility to HS. “Why does this seemingly healthy skin suddenly develop boils? And so I conduct my genetic studies because it gives us clues about what’s going wrong at a very fundamental level within skin cells. For instance, what are the proteins that are changing in there that are leading to disease?”
Hidradenitis suppurativa — also called acne inversa — is a skin disease that causes nodules (painful lumps) under the skin that can become abscesses (pus-filled sores or lesions). HS is believed to be an immune-mediated condition.
“Normally, the immune system and the hair follicle interact to make sure everything is operating optimally. With HS, something goes wrong with those interactions. We can see that the hair follicles become clogged and the immune system becomes very active. Both parts of the system are doing unusual things leading up to the boil formation. We are still trying to figure out important details,” Dr. Petukhova said.
Research shows that HS may be linked to a number of factors, including abnormalities in sweat glands, hormone dysregulation, and genetic variations. Environmental risk factors include smoking and higher body weight.
“We still need to fit all of these pieces together in a way that we can say, ‘OK, this is the order. This is the first thing going wrong. This is the domino we need to focus on to prevent the chain of events.’ More information about genetic variants contributing to the process will help get us there,” Dr. Petukhova added.
Members of myHSteam often wonder, and worry, if they can pass HS to their children: “Can anyone here verify a hereditary link?” a member asked. “My mom had HS, and I do too. I now have a daughter, and I am concerned about her.”
The answer is not a simple yes or no. Dr. Petukhova explained that there is still much to be learned about HS genetics. While scientists have discovered some genetic variants that are strongly associated with HS, that doesn’t mean everyone with HS has one of these disease-causing variants.
“Most people who have HS do not have a disease variant, cannot pass on a gene to their child, and don’t have it because they inherited a gene,” Dr. Petukhova emphasized.
Even if you do have a gene variant associated with HS, it’s not a guarantee that you will pass it down. “Just because you have a disease variant, the way inheritance works, not every child you have will have that variant. Every child has a 50 percent chance of having that same genetic variant,” Dr. Petukhova noted.
In the event that a child does inherit an HS genetic variant from one — or even both — parents, that isn’t a guarantee that child will develop HS. “We now know that not every variant has the same effect in different people. For example, we know from studies of breast cancer that women in the same family can carry the same disease variant, but not all of those women will go on to get breast cancer,” Dr. Petukhova explained. “We see this happen with many different types of genetic diseases. So even if by chance your child inherits a genetic variant that is linked to HS, it may not cause HS.”
Dr. Petukhova also explained that every single person has variants in their DNA and that most of them do not cause any symptoms or disease.
Importantly, Dr. Petukhova said that any single gene typically has many different functions. She stressed that parents should not blame themselves if a child inherits a particular gene variant: “That gene that they passed on that makes them more susceptible to developing HS, for instance, could also give them a stronger immune system and help protect the child in a way that’s not obvious to us. And so we shouldn’t feel guilty about passing on genes to our child because we just don’t know enough information about what those genes are doing.”
Research shows that approximately 30 percent to 40 percent of people with HS have a family history of the condition. “The way that we interpret that is that there is definitely a genetic component to HS, right? There’s some set of variants or genes that increase the risk for it,” Dr. Petukhova said. “But you can have genetic variants that are influencing risk without causing disease.”
Dr. Petukhova went on to explain how it can be hard to distinguish between a genetic predisposition for HS and shared environmental factors: “The other thing about family members is that they share so much more than DNA, right? They share lifestyles, they share diets, they share chemical exposures, right? And so there’s all these other things that family members are sharing.”
Dr. Petukhova is keen on expanding genetic research on HS, saying that an understanding of genetic factors in disease is crucial for improving treatment and disease outcomes. HS genetic research can potentially help better identify phenotypes (different forms) of HS. “The disadvantage that we’re at with HS is that there hasn’t been a lot of genetic studies, so we haven’t been able to gain as much insight as other clinical areas have,” she said.
She described how an understanding of breast cancer genetics has helped make treatment much more precise. “The example that I love to use is that people with advanced breast cancer, if they carry a pathogenic [disease-causing] variant in a BRCA gene, we know that they are likely to have a good response to treatment with what’s called a PARP inhibitor,” Dr. Petukhova explained. “So it’s a very targeted treatment. We also know that for patients with advanced breast cancer who don’t have a pathogenic [mutation] in BRCA, PARP inhibition isn’t likely to help, so doctors have the opportunity to start treatment with a different medication that is more likely to work.”
Dr. Petukhova said researchers are just beginning to understand the genetics of HS. “My goal is to help get dermatology to the same place where oncology is in terms of leveraging information in the genome to improve health outcomes,” she said. “We’re still at the very early stages of sequencing for research, to try to define the genes that could be contributing to it.”
To learn more about HS genetics, Dr. Petukhova needs to collect genetic information from a large number of people. She described how someone might participate in a genetic study of HS and how genetic testing is conducted.
“In the genetic study that I’m running, participants go online and they complete a survey. I collect a lot of information about other health conditions that they have, because I think that comorbidities [coinciding illnesses] give us clues about what’s causing disease, or the different causes of HS. They complete this survey online, they consent, they agree to participate in genetic studies. I send them a saliva collection kit, which is basically a tube that they spit into and then send back — you know, very similar to the consumer genetic companies like 23andMe and Ancestry,” she said, “And then our research team analyzes it. It gets included in our studies.”
Genetic studies take time because researchers require large sample sizes to ensure they get an accurate perspective on the characteristics of a particular gene. “We need to look at thousands of genomes for those patterns to start to emerge,” said Dr. Petukhova.
If you are interested in learning more about participating in genetic research on HS, you can start by talking to your health care team about studies you may be eligible for. “We work with many dermatologists in the U.S., so it is possible that your doctor may already be working with us,” Dr. Petukhova said. “If not, you can participate online by visiting skindeepsurvey.com.”
On myHSteam, the social network for people with hidradenitis suppurativa and their loved ones, more than 34,000 members come together to ask questions, give advice, and share their stories with others who understand life with hidradenitis suppurativa.
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