Impact of SNP Variants in PON-1 or UGT1A1 on Iron Chelation Therapy Outcomes and Zinc Status in Thalassemia Major Patients

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.