Int J Med Sci 2014; 11(11):1147-1153. doi:10.7150/ijms.9412

Research Paper

Impact of Single Nucleotide Polymorphism in IL-4, IL-4R Genes and Systemic Concentration of IL-4 on the Incidence of Glioma in Iraqi Patients

Haidar A. Shamran1, 6, Subah J. Hamza2, Nahi Y. Yaseen3, Ahmad A. Al-Juboory4, Dennis D Taub5, Robert L. Price6, Mitzi Nagarkatti6, Prakash S. Nagarkatti6, Udai P. Singh6 ✉

1. Medical Research Unit, School of Medicine, University of AL-Nahrain Iraq, Baghdad
2. Biotechnology Department, School of Science, University of AL-Nahrain, Iraq, Baghdad
3. Iraqi National Cancer Center, University of AL-Mustansiriya, Iraq, Baghdad
4. Neuroscience Hospital, Neurosurgery, Iraq, Baghdad
5. Center for Translational Studies, Medical Services, VA Medical Center, Department of Veteran Affairs, Washington DC, USA
6. Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, SC, USA

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Shamran HA, Hamza SJ, Yaseen NY, Al-Juboory AA, Taub DD, Price RL, Nagarkatti M, Nagarkatti PS, Singh UP. Impact of Single Nucleotide Polymorphism in IL-4, IL-4R Genes and Systemic Concentration of IL-4 on the Incidence of Glioma in Iraqi Patients. Int J Med Sci 2014; 11(11):1147-1153. doi:10.7150/ijms.9412. Available from

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Glioma is the most common and believed to be one of the most aggressive tumors of the central nervous system (CNS) in humans. Very little information is available on the etiology and pathogenesis of these tumors to date. A significant gap remains in our current understanding of the molecular pathways involved in the genesis, progression and clinical behavior of these tumors. Recently, several single nucleotide polymorphisms (SNPs) have been identified in cytokine gene sequences, particularly within the promoter region of these genes, and have been shown to be associated with the development of different types of brain tumors. The present study investigates the association of C-33T SNP in the interleukin-4 (IL-4) gene with systemic IL-4 level and the S503P SNP in the IL-4R gene with the incidence of glioma.

Blood samples were collected from 100 histologically confirmed adult patients with glioma, and 30 apparently healthy individuals from the same area. DNA was extracted from each blood sample, and the IL-4 and IL-4R genes were amplified using polymerase chain reaction (PCR) with gene-specific primers. Systemic IL-4 concentration was assessed in serum samples from each participant by enzyme-linked immunosorbent assay (ELISA). We observed a negative association between the homozygous genotype (CC) of the SNP C-33T of the IL-4 gene with the incidence of glioma (OR=0.19, 95% CI=0.035-1.02), while the T allele of the SNP demonstrated a significant protective association against glioma. Similarly, the heterozygous (CT) and homozygous mutant (CC) of the SNP S503P of the IL-4R gene demonstrated a significant association with glioma development (OR=0.405, 95% CI=0.17-0.969 and OR=0.147, 95% CI=0.036-0.6 respectively), while the C allele exhibited a highly significant association with protection from glioma formation.

These findings suggest that the T allele of the SNP C-33T in the IL-4 gene and the C allele of the SNP S503P in IL-4R may have a protective role against glioma development.

Keywords: Single nucleotide polymorphism (SNPs), interleukin-4, interleukin-4R, brain tumor, and Glioma