Impact of SNP Variants in PON-1 or UGT1A1 on Iron Chelation Therapy Outcomes and Zinc Status in Thalassemia Major Patients
Journal
Biological Trace Element Research
ISSN
1559-0720
Date Issued
2025-09-23
Author(s)
Lu, Meng-Yao
Tsai, Wan-Fu
Wu, Chang-Shiann
Wang, Chien-Sheng
Syifa, Nailis
Lu, Mong-Liang
Liao, Jiahn-Haur
Lin, Kai-Hsin
Wu, Tzu-Hua
Abstract
Factors affecting iron chelation therapy outcomes are complex and should be identified to tailor interventions to the needs of individuals with beta-thalassemia major (TM). The purpose of the study was to determine the effects of PON-1 or UGT1A1 single-nucleotide polymorphisms on therapeutic outcomes via deferasirox (DFX) and the antioxidant status. PON-1 (rs662) or UGT1A1 (rs887829) polymorphisms, iron chelation therapy outcomes (cardiac iron T2*, serum ferritin (SF)), and antioxidant-related nutritional indices (PON-1 activity, zinc, 25-hydroxyvitamin D) were determined in 44 Taiwanese TM patients receiving chronic blood transfusion and DFX therapy. Patients' cardiac iron T2* values were negatively correlated with SF levels (r = - 0.38, p < 0.01). PON-1 AA/AG carriers had significantly greater PON-1 activity, whereas PON-1 GG carriers were prescribed significantly higher DFX doses. UGT1A1 CT and TT carriers had marginally significantly greater SF levels. Only four patients had normal levels of 25-hydroxyvitamin D (25(OH)D > 30 ng/mL). PON-1 activity in those with SF > 2500 (6.4 ± 1.9 units/mL) was significantly lower than that (7.7 ± 1.7 units/mL; p < 0.03) in patients with SF ≤ 2500. Although not statistically significant, variants in PON-1 or UGT1A1 were associated with increased odds ratios (2.44 and 2.899, respectively) for lower cardiac iron T2* values < 30 ms. Taiwanese TM patients with moderate iron overload status had significantly lower PON-1 activity and vitamin 25(OH)D levels, particularly those with T2* < 30 ms. Patients with PON-1 GG and UGT1A1 TT carriers may have an increased risk of cardiac iron overload.
Subjects
Beta-thalassemia major
Iron chelation outcomes
PON-1 activity
Polymorphisms
Vitamin D
Zinc
Publisher
Springer Science and Business Media LLC
Type
journal article