High Frequency of Glucose-6-Phosphate Dehydrogenase Deficiency in Patients Diagnosed with Celiac Disease

Celiac disease (CD) is characterized by a proinflammatory state associated with the production
of reactive oxygen species, i.e., a condition of oxidative stress. In this study, we tested the
hypothesis that the inherited deficiency of glucose-6-phosphate dehydrogenase (G6PD), by causing
impaired antioxidant defense, may increase the risk of CD. Methods: A retrospective monocentric
case-control study was performed using the clinical records of 8338 outpatients (64.6% women) scheduled
for upper endoscopy between 2002 and 2021 in Northern Sardinia. Overall, 627 were found
to have CD (7.5%), and 1027 resulted to be G6PD-deficiency carriers (12.3%). Since randomization
was impractical, the potential covariates imbalance between cases and controls was minimized using
a 1:2 propensity-score-matched (PSM) analysis. Results: Overall, G6PD deficiency was associated
with increased risk of CD (odds ratio (OR) 1.50; 95% confidence interval (CI) 1.19–1.90). The PSM
procedure identified 1027 G6PD-deficient and 2054 normal patients. Logistic regression including the
propensity score detected for G6PD deficiency an OR of 1.48 (95%CI 1.13–1.95; p = 0.004). Conclusions:
Our findings show that the enzyme defect was significantly and positively associated with CD, in
line with the pro-oxidant impact of the enzyme defect observed in animal models and humans.