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Title:	Interleukin-1 receptor antagonist gene polymorphisms and its association with disease activity and joint damage in Malaysian rheumatoid arthritis patients
Authors:	Omimah Khaled Jaber Nofal (P75180)
Supervisor:	Endom Ismail, Assoc. Prof. Dr.
Keywords:	Rheumatoid arthritis Rheumatoid arthritis -- Diagnosis Rheumatoid arthritis -- Treatment. Universiti Kebangsaan Malaysia -- Dissertations Dissertations, Academic -- Malaysia
Issue Date:	16-Feb-2019
Description:	Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis. The underlying pathogenesis of RA are related to antigen driven helper T-lymphocytes that stimulate a cascade of cytokine production involving interleukin 1, 6, 12, 17 and TNFα. The classical Interleukin -1 (IL-1) family is composed of three major proteins, namely IL-1α, IL-1β and receptor antagonist (IL-1RA). IL-1RA antagonizes the biological activities of IL-1α and IL-1β. In vitro studies of RA indicate that IL-1 can cause cartilage destruction by stimulating the production of matrix metalloproteinases by blocking the repair processes of the cartilage. Thus, the main objective of this study is to investigate the relationship between two polymorphisms of IL-1RA i.e. +2018 and varible number tandom repeat (VNTR) with clinical characteristics of RA. DNA samples from 18 healthy controls and 77 RA patients were obtained for this study. Levels of IL-1α, IL-1β and matrix metalloproteinases 3 (MMP3) were determined by the enzyme-linked immunosorbent assay (ELISA). Genotyping for +2018 and VNTR were done using polymerase chain reaction (PCR) and direct sequencing. The mean serum levels (pg/mL) for IL-1α, IL-1β and (ng/mL) for MMP3 are significantly (p<0.05) much higher among patients: (562.9 ± 160.7); (598.5 ± 171.2); and (82.8 ± 8.14) compared to controls: (0.77 ± 0.43); (0.95 ± 0.45); and (31.4 ± 3.28). The frequency of the +2018 genotypes, T/T and C/T did not differ between the patients and the controls. So as L/L, L/2 and 2/2 genotypes for VNTR. The C/T genotype had a significant link with higher average readings for the erythrocyte sedimentation rate (ESR); swollen joint counts; disease activity in 28 joints (DAS28) for disease activity; and modified sharp score (MSS) for disease damage. L/2 genotype for VNTR almost had the same significant clinical associated features with C/T genotype, except for swollen joint damage. In conclusion, +2018 and VNTR polymorphism in the IL-1RA gene are the non-causative but an important genetic marker where its strongest link with RA were repeatedly shown by their respective C/T genotype and allele 2 suggesting the use of C/T genotype and allele 2 as prognostic markers for advanced progression, highly aggressive and the more severe form of rheumatoid arthritis.,Master of Science
Pages:	80
Call Number:	RC933.N643 2019 tesis
Publisher:	UKM, Bangi
Appears in Collections:	Faculty of Science and Technology / Fakulti Sains dan Teknologi

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