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<p>Beta-thalassemia is an inherited disorder of hemoglobin which leads to severe anemia and the complications of oxidative stress. The FAS/FASL apoptotic pathway is important to erythropoiesis at several levels; however, their the genetic associations with beta-thalassemia remain unclear. The aim of study was determining the possible relation of FAS (rs2234767) and FASL (rs5030772) polymorphisms with beta-thalassemia and oxidative stress in the Iraqi population. This is a case–control study conducted with 450 patients with beta-thalassemia and 450 healthy controls from Al-Qadisiyah Province, Iraq. Genetic polymorphisms were examined through T-ARMS PCR and validated with Sanger sequencing. Serum levels of certain antioxidant enzymes (SOD, CAT, GST) were also measured by ELISA. Other relevant biochemical parameters such as ferritin, some liver enzymes, and some hematological indices were examined as well. There were notable changes in the polymorphisms of FAS and FASL with beta-thalassemia (<i>p</i>&#xa0;= 0.038 and <i>p</i>&#xa0;= 0.026, respectively). Patients had greater FAS AA genotypes (OR&#xa0;= 4.0, 95% CI 2.1–7.6, <i>p</i>&#xa0;= 0.015) and FASL GG genotypes (OR = 6.9, 95% CI 1.4–33.5, <i>p</i> = 0.009). Haplotype analysis showed that the combination of FAS-A and FASL-G conferred the highest risk for the disease (OR&#xa0;= 2.014, 95% CI 1.289–3.146, <i>p</i>  = 0.002). Patients also showed higher levels of antioxidant enzymes: SOD&#xa0;= 108.8 ± 11.84, CAT  =  333.7 ± 38.20, and GST = 9.069 ± 1.045, all <i>p</i>&#xa0;&lt; 0.005. We conclude that there is an association between variants in the FAS/FASL genes and the risk of developing beta-thalassemia and they are linked with high levels of oxidative stress, indicating that these polymorphisms may enhance the disease through disruption of apoptotic processes and increased oxidative stress.</p>

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Genetic Polymorphisms in FAS/FASL Apoptotic Pathway Genes Modulate Beta-Thalassemia Susceptibility and Oxidative Stress Response: A Case–Control Study

  • 期刊论文

  • 发表日期：

    2025年8月30日

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  • Doaa H. Chyad,
  • Wisam H. Hoidy,
  • Aws Rassul Hussain Al-Salih

摘要

Beta-thalassemia is an inherited disorder of hemoglobin which leads to severe anemia and the complications of oxidative stress. The FAS/FASL apoptotic pathway is important to erythropoiesis at several levels; however, their the genetic associations with beta-thalassemia remain unclear. The aim of study was determining the possible relation of FAS (rs2234767) and FASL (rs5030772) polymorphisms with beta-thalassemia and oxidative stress in the Iraqi population. This is a case–control study conducted with 450 patients with beta-thalassemia and 450 healthy controls from Al-Qadisiyah Province, Iraq. Genetic polymorphisms were examined through T-ARMS PCR and validated with Sanger sequencing. Serum levels of certain antioxidant enzymes (SOD, CAT, GST) were also measured by ELISA. Other relevant biochemical parameters such as ferritin, some liver enzymes, and some hematological indices were examined as well. There were notable changes in the polymorphisms of FAS and FASL with beta-thalassemia (p = 0.038 and p = 0.026, respectively). Patients had greater FAS AA genotypes (OR = 4.0, 95% CI 2.1–7.6, p = 0.015) and FASL GG genotypes (OR = 6.9, 95% CI 1.4–33.5, p = 0.009). Haplotype analysis showed that the combination of FAS-A and FASL-G conferred the highest risk for the disease (OR = 2.014, 95% CI 1.289–3.146, p  = 0.002). Patients also showed higher levels of antioxidant enzymes: SOD = 108.8 ± 11.84, CAT  =  333.7 ± 38.20, and GST = 9.069 ± 1.045, all p < 0.005. We conclude that there is an association between variants in the FAS/FASL genes and the risk of developing beta-thalassemia and they are linked with high levels of oxidative stress, indicating that these polymorphisms may enhance the disease through disruption of apoptotic processes and increased oxidative stress.