You inherit characteristics like eye color and height from your parents — and sometimes, you also inherit your risk of certain diseases. These include primary biliary cholangitis (PBC), an autoimmune condition that used to be called primary biliary cirrhosis. PBC isn’t considered a hereditary disease, but certain genetic factors may make you more likely to develop it.

This article discusses what researchers know about the possible genetic link to PBC and looks at other common risk factors, such as environmental triggers. Your doctor can help you better understand your risk of PBC and whether you should be monitored for the disease.

Understanding the Genetics of Primary Biliary Cholangitis

Your genes are like an instruction manual your body uses to make proteins and function properly. In many hereditary diseases, a specific gene mutation (change) that causes the condition is passed from parent to child. This happens because children inherit half of their genes from each parent.

However, PBC isn’t caused by a single gene change. Instead, this condition develops from a combination of gene changes and environmental factors.

Family History and PBC

Studies show that having a family history of PBC raises your risk of the disease. If you have a first-degree relative — like a parent or sibling — with PBC, you’re 100 times more likely to develop it than someone without that family history.

One published report described four sisters who all developed PBC. The authors believed the risk was passed down through their mother, because the sisters also had a half-sister (same father) who didn’t have the disease.

Still, having a relative with PBC doesn’t mean you’ll definitely get it. Other factors also play a role in your risk. You can talk more with your doctor about your risk and what you can do to lower it.

Female Sex and Risk of PBC

According to Mayo Clinic, women are much more likely than men to develop PBC. Most females have two X chromosomes, and most males have one X and one Y chromosome. However, not everyone fits into this pattern. Some people have different chromosome combinations due to genetic conditions or other biological differences.

Researchers have looked into how the X chromosome might affect the development of PBC. Sex hormones such as estrogen may also play roles. However, more research is needed to understand how these factors might contribute to PBC risk.

Other Autoimmune Diseases

PBC is an autoimmune disease that damages the small bile ducts in the liver. The immune system mistakenly attacks these ducts, causing inflammation that blocks the flow of bile acid. Over time, this can lead to fibrosis (scarring) and permanent liver damage. Some people eventually develop liver failure and may need a liver transplant.

Research shows that people with PBC often have other autoimmune conditions. In one study of 1,090 people with PBC, 32 percent also had another autoimmune condition, compared with just 13 percent of people without PBC.

There may be a genetic link between certain autoimmune diseases and PBC. Many of these conditions involve changes in similar genes that affect how the immune system works. Some autoimmune diseases that often occur with PBC include:

• Sjögren’s disease (formerly called Sjögren’s syndrome) — Causes dry eyes and dry mouth by attacking glands that make moisture
• Systemic lupus erythematosus — Can cause joint pain, fatigue, and inflammation throughout the body
• Rheumatoid arthritis — Leads to painful swelling and stiffness in the joints
• Autoimmune thyroid disease — Affects how the thyroid gland controls energy and metabolism
• Scleroderma — Causes thickening and tightening of the skin and sometimes affects internal organs

Gene Changes Linked to PBC

No single specific gene is responsible for PBC, but researchers have found around 70 gene loci (locations on chromosomes) that may raise a person’s risk. Many of these gene changes affect how the immune system functions, which makes sense since PBC is an autoimmune condition.

Researchers have found that many of these genes are involved in the production or regulation of key immune system components, such as:

• Human leukocyte antigens — Proteins that help the immune system tell the difference between the body’s own cells and harmful invaders
• Interleukins — A group of proteins that trigger inflammation and help activate immune responses
• B cells — A type of immune cell that produces antibodies (immune system proteins), which in PBC may mistakenly attack healthy liver tissue

Researchers are still looking into gene patterns to understand their roles in PBC and whether they could help predict who’s most at risk.

Environmental Risk Factors Linked to PBC

If your genes may make you more likely to develop PBC, certain environmental factors may further raise your risk. The good news is that most of these factors are modifiable, meaning you can take steps to avoid them.

Exposure to Toxic Chemicals

It’s well known that cigarette smoke contains thousands of chemicals, many of which are harmful. Studies now show that smoking raises the risk of PBC. One review involving more than 21,000 people showed that participants who smoked had a 31 percent higher risk of PBC compared to those who never smoked.

Other chemicals that may increase your chances of PBC include hair dye and nail polish. These products contain substances called xenobiotics, which can change the structure of your body’s proteins. Your immune system may mistake these proteins as foreign and attack them, triggering an autoimmune response and leading to diseases like PBC.

Your doctor will likely advise you to avoid tobacco products. You can also reduce chemical exposure by not using nail polish or hair dye.

Frequent Urinary Tract Infections

Many people with PBC have a history of urinary tract infections (UTIs). These infections develop when bacteria, such as E. coli, enter the urethra and spread to the bladder and kidneys.

Certain proteins in E. coli resemble proteins in the human body. This can confuse the immune system, causing it to attack your healthy tissues — a process called molecular mimicry. In people already prone to autoimmune disease, this may lead to PBC.

If you tend to have frequent UTIs, talk to your doctor. They may suggest ways to reduce your risk, such as:

• Taking low-dose antibiotics to keep bacteria from growing
• Urinating (peeing) often to get rid of bacteria in your bladder
• Drinking plenty of water to help your body clear bacteria

Understanding Your Risk of PBC

PBC isn’t considered a hereditary disease caused by one specific gene mutation. Instead, it’s a complex condition linked to a combination of genetic changes and environmental factors. Because there’s no one gene change to look for, doctors generally don’t recommend genetic testing for PBC.

If you have a family history of PBC, it’s important to keep an eye on your liver health. Your doctor may suggest routine blood tests to check liver function. One key test checks the level of alkaline phosphatase (ALP), an enzyme that rises in people with liver diseases. Regular monitoring can help diagnose PBC in the early stages, before serious liver damage sets in.

Your doctor can also do tests to look for antibodies, especially antimitochondrial antibodies (AMA). According to the American Liver Foundation, nearly everyone with PBC has AMA in their blood. If you have a family member with PBC, elevated ALP and AMA levels could be an early sign of the disease.

Find Your Team

On myPBCteam, the social network for people living with primary biliary cholangitis and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with PBC.

Are you living with PBC? Do you have family members who also have the disease? Do you have other risk factors linked to PBC? Share your story in the comments below, or start a conversation by posting on your Activities page.