TITLE:
Analysis of Association between Interleukin-6 (IL6), Interleukin-13 (IL13) and Tumor Necrosis Factor-Alpha (TNF-alpha) Gene Polymorphisms and Genetic Susceptibility of Rheumatoid Arthritis in Kuwaiti Arab
AUTHORS:
Adel M. Al-Awadhi, Mohammad Z. Haider, Aminah M. Al-Awadi, Anita K. Kalarikkal, Jalaja Sukumaran, Eman A. H. Hasan, Youssef Bartella
KEYWORDS:
Genotype, Cytokine Gene, Polymorphism, Rheumatoid Arthritis, Kuwait
JOURNAL NAME:
Open Journal of Rheumatology and Autoimmune Diseases,
Vol.12 No.4,
October
21,
2022
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.