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<p>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 <i>PON-1</i> or <i>UGT1A1</i> single-nucleotide polymorphisms on therapeutic outcomes via deferasirox (DFX) and the antioxidant status. <i>PON-1</i> (rs662) or <i>UGT1A1</i> (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 (<i>r</i> =  − 0.38, <i>p</i> &lt; 0.01). <i>PON-1</i> AA/AG carriers had significantly greater PON-1 activity, whereas <i>PON-1</i> GG carriers were prescribed significantly higher DFX doses. <i>UGT1A1</i> CT and TT carriers had marginally significantly greater SF levels. Only four patients had normal levels of 25-hydroxyvitamin D (25(OH)D &gt; 30&#xa0;ng/mL). PON-1 activity in those with SF &gt; 2500 (6.4 ± 1.9 units/mL) was significantly lower than that (7.7 ± 1.7 units/mL; <i>p</i> &lt; 0.03) in patients with SF ≤ 2500. Although not statistically significant, variants in <i>PON-1</i> or <i>UGT1A1</i> were associated with increased odds ratios (2.44 and 2.899, respectively) for lower cardiac iron T2* values &lt; 30&#xa0;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* &lt; 30&#xa0;ms. Patients with <i>PON-1</i> GG and <i>UGT1A1</i> TT carriers may have an increased risk of cardiac iron overload.</p>

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

  • 期刊论文

  • 发表日期：

    2025年9月23日

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  • Meng-Yao Lu,
  • Wan-Fu Tsai,
  • Chang-Shiann Wu,
  • Chien-Sheng Wang,
  • Nailis Syifa,
  • Mong-Liang Lu,
  • Jiahn-Haur Liao,
  • Wei J. Chen,
  • Kai-Hsin Lin,
  • Tzu-Hua Wu

摘要

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.