Cystic fibrosis carriers — individuals who have certain genetic mutations in one of the copies of the CFTR gene — have a significantly increased risk compared with healthy people for several CF-related conditions, a new study shows.
The study, “Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions,” was published in the journal Proceedings of the National Academy of Sciences.
Because CF is a recessive genetic disorder, both copies of a person’s CFTR gene — one inherited from the mother and the other from the father — must be mutated to develop the full-blown disease. People with CF develop recurrent pulmonary infections and also hormonal, gastrointestinal, pancreatic, liver, and reproductive problems.
People with one mutated copy of the CFTR gene are called CF carriers. It was believed that these individuals, “having only 1 defective CFTR gene, are not considered to be at increased risk for CF-related conditions,” the researchers said.
In fact, “CF carriers are routinely informed that they are not at increased health risk,” they said.
“However, some studies have found a higher-than-expected proportion of CF carriers with a limited number of CF-related conditions,” the team noted. These conditions include pancreatitis, male infertility, airway infections, and gastrointestinal problems.
The researchers noted that the majority of these studies were performed on a small scale and lack appropriated controls. Thus, there was an unmet need “to confirm and expand on previous studies suggesting that CF carriers are at greater risk for CF-related conditions.”
That led the team, from the University of Iowa (UI), to investigate the risk of carrier status in developing CF-related conditions. The scientists analyzed data from the IBM Watson/Truven Health Analytics MarketScan Database, a large database of health information.
The team identified 19,802 CF carriers, and matched each carrier with five people without CF (controls), totaling 99,010 people. For the CF group, they included 23,557 patients with the disease, who were matched to a non-CF group of 117,762 healthy people (controls).
All participants were analyzed for 59 CF-related conditions, including those affecting the bone, like osteoporosis and scoliosis, those impacting the endocrine system, including diabetes, those having an effect on the gastrointestinal system, and those affecting organs like the liver, pancreas, kidneys, and lungs.
The results showed that CF carriers were at higher risk for all 59 conditions analyzed, with a significant risk found for 57 of them.
Carriers had a significantly greater risk of conditions previously linked to the CF carrier status, like male infertility or pancreatitis. However, they also were found to be at significantly increased risk for conditions not previously linked to the carrier state, such as constipation or diabetes, among others.
Moreover, the team found that the more prevalent a condition is in CF patients, the more widespread it also is in CF carriers.
To exclude any potential bias, the researchers included a “CF carrier validation cohort” — a group composed of 2,185 mothers of CF patients (meaning the mothers must be CF carriers).
Health records of these women, from before their children were diagnosed, mirrored the previous findings. Specifically, among the 42 conditions detected in the adult women, 40 of them had higher prevalence among CF carriers. For 28 of these conditions, the link was statistically significant.
“Taken together, our results call into question the idea that CFTR expression levels associated with the CF carrier state are sufficient to completely protect subjects from CF-related conditions,” the researchers said.
Notably, while the investigators said their findings show the risk of certain CF-related conditions is higher for carriers compared with healthy controls (relative risk), the actual chance (absolute risk) of developing these conditions is still very low.
“CF carriers are nowhere near as at-risk as patients with CF,” Philip Polgreen, MD, UI professor of internal medicine and epidemiology, and the study’s lead author, said in a press release. “But compared to people with no CF mutations, they have a slightly higher risk for some diseases.”
“For conditions such as chronic pancreatitis, the relative risk is very high for carriers, but the absolute risk of pancreatitis is low, even for CF carriers in our sample,” the researchers said.
Nonetheless, these findings carry implications for how CF carriers — including more than an estimated 10 million Americans — live their lives. For example, “being a CF carrier may provide motivation for avoiding other disease-risk factors, such as excessive alcohol use (e.g., pancreatitis), and may help inform screening or preventive-treatment strategies (e.g., gastrointestinal cancer),” the researchers said.
The team also emphasized that genetic testing, combined with data from large medical databases, may help CF carriers, and be extended to carriers of other recessive genetic diseases.
“More and more individuals are receiving genetic testing from their providers or from private companies, and if this information can be incorporated into healthcare records, there could be many new opportunities to discover both population-level health risks and individualized treatment options,” said Aaron Miller, PhD, UI assistant professor of epidemiology, and the study’s first author.