ASSOCIATION OF INTERLEUKIN-6, INTERLEUKIN-4, AND TUMOR NECROSIS FACTOR-ALPHA GENE POLYMORPHISMS WITH SERUM CYTOKINE PROFILES IN BETA-THALASSEMIA MAJOR PATIENTS
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Thalassemia, Interleukin-6, Interleukin-4, Tumor necrosis factor-alpha, Single nucleotide polymorphism
Abstract
Beta Thalassemia is an inherited condition results from mutation in β globin gene which leads to several complication including, severe anemia and iron overload among others, in which the signs appear in early childhood. This study investigated the possible role of cytokine gene polymorphism on thalassemia patients. Our research involved 72 patients diagnosed with beta thalassemia major and a control group of 40 cases. Both groups' ages ranged from 1 to 30 years. Serum cytokines IL-6, IL-4, and TNF-α level were measured using enzyme linked immunosorbent assay (ELISA) as well as analyzing the genetic profile for the same genes. Blood samples were subjected to DNA isolation and molecular detection for gene polymorphism (interleukin 6 polymorphism at position 174, interleukin 4 polymorphisms at position 589, and tumor necrosis factor alpha polymorphism at position 308) using ARMS-PCR. Results showed significant increase in IL-6 and TNF-α (p<0.05), whereas the difference in IL-4 was not significant. High-producing genotypes (GG for IL-6, and GG for TNF-α) showed the highest serum cytokine levels, while low-producing genotypes (CC, and AA respectively) showed the lowest. Serum IL-6 levels were significantly higher in patients across all IL-6 genotypes (GG, GC, CC) compared to their respective genotype-matched healthy controls. IL-4 decreased in CC and slightly increased in CT (not significantly). TNF-α levels significantly increased in GG and GA, but not in AA. For the IL-6 (-174G>C) polymorphism, the odds ratio for the GC genotype was 0.66 (95% CI: 0.27–1.61), whereas the odds ratio for the CC genotype was 1.42 (95% CI: 0.22–15.52). The CC, CT, and TT genotypes displayed varying frequencies among groups in the IL-4 gene polymorphism. In relation to the TNF-α gene polymorphism, the AA genotype displayed an odds ratio of 1.7 (95% CI: 0.13–91.27), while the large confidence interval suggests poor statistical precision, whereas the GG genotype was not substantially linked to thalassemia.
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