High GGT levels raise SSc risk by nearly 2 times, Korean study finds

GGT enzyme works to generate free radicals that damage cells

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Elevated levels of the gamma-glutamyl transferase (GGT) enzyme — involved in oxidative stress, a result of insufficient antioxidant defenses against toxic free radicals — were associated with a higher risk of developing scleroderma, a large South Korean study reports.

“These findings could lead to a closer monitoring for high risk individuals and an earlier diagnosis and treatment,” the scientists wrote.

The study, “Higher gamma-glutamyl transferase levels are associated with an increased risk of incident systemic sclerosis: a nationwide population-based study” was published in the journal Scientific Reports.

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Scleroderma is caused by an overactive immune system that mistakenly attacks the body’s tissues, which leads to hardening and fibrosis — scarring — of the skin. The disease, also known as systemic sclerosis (SSc), can affect internal organs.

Accumulating evidence indicates that oxidative stress contributes to several features of SSc. In oxidative stress, free radicals, or reactive oxygen species (ROS), are harmful to cells.

The GGT enzyme is involved in the generation of ROS, and its activity has been linked with cardiovascular conditions, neurological diseases, and cancer.

But scientists do not know if GGT levels correlate with the risk of scleroderma development.

Researchers in Seoul analyzed data from the Korean National Health Insurance Service claims database to identify adults, ages 20 and older, without SSc at the time of a 2009 national health examination (required every two years in South Korean for adults starting at age 40 and for all employed workers). People were followed from 2009 through 2019 with exams that recorded GGT levels as well as more common health measures, like blood pressure and smoking status.

In total, the study’s analysis involved about 6.1 million people, and found that 654 developed SSc after a mean follow-up of 9.2 years.

People then were divided into four groups according to their mean levels of GGT: group one had 12.75 international unites per liter (IU/L) of the GGT enzyme; group two, 19.45 IU/L; group three, 26.77 IU/L; and group four, 54.38 IU/L.

Those with higher GGT levels, in general, were older and had a higher body mass index (BMI), a measure of body fat. They also were more likely to be in a low income group, be current smokers and heavy alcohol drinkers, and less likely to exercise regularly. Rates of high blood pressure, type 2 diabetes, fat imbalance in the blood, and chronic kidney disease also were more common in the higher GGT level group.

An initial statistical analysis found a significantly higher incidence (new cases) of SSc among people with elevated GGT levels. Specifically, the risk of SSc was 1.72 times higher for those in the highest GGT level group (group four) compared with people in group one.

Similar results were seen in a multivariate analysis — which considers multiple variables resulting in one outcome — that adjusted for the presence of additional disorders, age, sex, BMI, economic income, smoking status, alcohol consumption, and physical activity.

A subgroup analysis by sex found the risk of SSc to be 2.48 times higher for men in group four than for women also in that high GGT group.

“Our data suggest that individuals with higher levels of GGT could be considered as having an increased risk of developing SSc,” the researchers concluded. “Clinicians should be aware that close monitoring for the development of SSc is warranted in individuals with higher GGT levels.”

Among noted study limitations was data drawn solely from the Korean population, so its findings may not be widely applicable.