Study reveals elevated gamma-glutamyl transferase levels linked to higher risk of systemic sclerosis development

Systemic sclerosis (SSc) stands as a chronic immune-mediated disease with highest mortality rates among all rheumatic diseases. Prompt detection of SSc and the timely initiation of treatment play pivotal roles in achieving improved outcomes. A recent scientific nationwide population study underscores that elevated levels of gamma-glutamyl transferase (GGT) correlate with an increased risk of developing incident SSc.

The research, conducted by Kwon and collaborators, involved a cohort from the Korean National Health Insurance Service database. This cohort comprised individuals free from SSc who underwent a national health examination in 2009. Over a mean observation period of 9.2 years, the incidence rate of SSc was calculated at 1.16 per 100,000 person-years.

The study categorized GGT levels measured in 2009 into quartiles (Q1 being the lowest and Q4 the highest) among 6,091,788 participants. After meticulous adjustments for various factors including age, sex, body mass index, income, lifestyle habits, and health conditions like hypertension and diabetes, the findings revealed a significant correlation between higher quartiles of GGT levels and an increased risk of incident SSc. Notably, the highest quartile (Q4) displayed an adjusted hazard ratio (aHR) of 1.807 (95% confidence interval CI 1.446-2.259), highlighting a substantial association. The Q3 and Q2 also exhibited increased risk to a lesser extent (Q3: aHR 1.221, 95% CI 0.971-1.536; Q2: aHR 1.034, 95% CI 0.807-1.324; p for trend < 0.001).

GGT has long been used as a serum marker to identify alcohol-related liver and hepatobiliary diseases. Recent research has unveiled its role in enhancing the production of reactive oxygen species (ROS). This pro-oxidant behavior has led to the exploration of the GGT’s involvement in various conditions, including cardiovascular ailments, cancers, lung inflammation, and neurological disorders.

However, there is a notable gap in understanding how GGT might relate to SSc, a condition where oxidative stress plays a pivotal role in its development. Presently, there is a lack of studies investigating the potential connection between GGT and SSc. Considering the significant role oxidative stress plays in SSc’s pathogenesis, exploring GGT as a potential marker associated with the onset of SSc holds promise for future research.

The current study suggests that individuals displaying elevated levels of GGT might face increased risk of developing SSc. This underscores the importance of clinicians to remain vigilant and consider close monitoring for SSc development among those with higher GGT levels. Such proactive measures could pave the way for early diagnosis and prompt initiation of treatment for SSc, potentially improving patient outcomes.


Kwon OC, Han K, Park MC. Higher gamma-glutamyl transferase levels are associated with an increased risk of incident systemic sclerosis: a nationwide population-based study. Sci Rep. 2023 Dec 11;13(1):21878.