Interleukin-4 Genetic Polymorphisms Predict Susceptibility to Childhood Acute Lymphoblastic Leukemia.
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BACKGROUND/AIM: Interleukin-4 (IL-4) is a key T-helper 2 cytokine involved in immune regulation, allergic responses, and hematological malignancies. Although aberrant IL-4 expression has been implicated in acute lymphoblastic leukemia (ALL), the contribution of IL-4 genetic polymorphisms to childhood ALL susceptibility has never been investigated. This study investigated the associations of IL-4 rs2243248 (T-1099G), rs2243250 (T-589C), and rs2070874 (T-33C) genotypes with childhood ALL risk in a Taiwanese population. MATERIALS AND METHODS: The study was conducted at China Medical University Hospital (Taichung, Taiwan), involving 266 children diagnosed with ALL and 266 age- and sex-matched cancer-free controls. Genotypes of IL-4 rs2243248, rs2243250, and rs2070874 were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Odds ratios (ORs) and 95% confidence intervals (CIs) in addition to chi-square tests were utilized to evaluate the potential association. RESULTS: The genotypic distributions of all three IL-4 polymorphisms in controls conformed to Hardy-Weinberg equilibrium (all p>0.05). For rs2243248, neither the GT genotype (OR=1.18, 95%CI=0.73-1.92, p=0.5836) nor the GG genotype (OR=2.07, 95%CI=0.51-8.39, p=0.3341) was significantly associated with childhood ALL susceptibility. Similarly, rs2243250 CT (OR=1.18, 95%CI=0.82-1.71, p=0.4324) and CC genotypes (OR=1.93, 95%CI=0.83-4.49, p=0.1790) showed no significant effects. For rs2070874, both CT (OR=0.92, 95%CI=0.64-1.33, p=0.7294) and CC genotypes (OR=0.83, 95%CI=0.37-1.84, p=0.7936) were unrelated to ALL risk. Allelic analyses yielded consistent findings, with no significant associations observed for rs2243248 (OR=1.29, 95%CI=0.84-1.97, p=0.2823), rs2243250 (OR=1.27, 95%CI=0.95-1.72, p=0.1294), or rs2070874 (OR=0.91, 95%CI=0.68-1.23, p=0.5962). CONCLUSION: This first investigation of IL-4 genetic polymorphisms in childhood ALL demonstrated that rs2243248, rs2243250, and rs2070874 are not significantly associated with childhood ALL susceptibility in Taiwanese individuals. These findings suggest that common IL-4 promoter variants are unlikely to be major genetic determinants of childhood ALL risk, although larger studies in diverse populations are warranted to validate these observations.