Analysis of Association between Interleukin-6 (<i>IL</i>6), Interleukin-13 (<i>IL</i>13) and Tumor Necrosis Factor-Alpha (<i>TNF-alpha</i>) Gene Polymorphisms and Genetic Susceptibility of Rheumatoid Arthritis in Kuwaiti Arab

Abstract

Background: Rheumatoid arthritis (RA) is a common autoimmune disease in which a combination of risk alleles from different susceptibility genes predisposes the patients to develop clinical symptoms following exposure to environmental factors. RA is a chronic and progressive disease characterized by synovial inflammation that results in destruction in the affected joints and severe problems in individual’s mobility. Several immune-related risk factors have been associated with RA, these include single nucleotide polymorphisms (SNPs) in cytokine genes. The impact of these cytokine gene polymorphisms is due to their association either with elevated serum levels and/or variations in their serum levels are associated with disease-onset and progression. The objective of this study was to investigate the role of Interleukin-6 (IL6), Interleukin-13 (IL13) and Tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms in genetic susceptibility of RA in Kuwaiti patients. Methods: We have determined the genotypes of IL6 gene (-174G/C; rs1800795), IL13 gene (R130Q; rs20541) and TNF-alpha gene (-308A/G' rs1800629) polymorphisms in 192 Kuwaiti patients with RA and compared it to that in 104 healthy controls. The diagnosis of RA was based on the American College of Rheumatology (ACR) classification criteria. The genotypes for IL6, IL13 and TNF-alpha gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods and confirmed by DNA sequencing. Results: The frequency of IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G' rs1800629) polymorphisms manifested a statistically significant difference between Kuwaiti RA patients and controls (P = 0.02 and 0.002 respectively). In contrast, the frequency of IL13 gene (R130Q; rs20541) polymorphism did not show a significant difference between Kuwaiti RA patients and controls. Conclusions: Our data showed an association of two cytokine gene polymorphisms (i.e. IL6 gene -174G/C; rs1800795 polymorphism, and TNF-alpha gene -308A/G, rs1800629 polymorphism) with RA in Kuwaiti patients highlighting their significant contribution in genetic susceptibility of this chronic disease possibly along with other factors.