الفهرس 
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Abstract
Rheumatoid arthritis (RA) is one of the most common human systemic autoimmune diseases. It is characterized by chronic inflammation of the joint, which may lead to structural damage of the cartilage and bone. The worldwide prevalence of RA is about 1% and the precise etiology is still unknown.
RA is a heterogeneous disease with a complex genetic component. Previous studies identified multiple genetic regions that might be associated with RA. Further studies have demonstrated that multiple autoimmune diseases may share common susceptibility genes. Therefore, susceptibility genes associated with other autoimmune diseases may be candidates in the study of gene susceptibility to RA.
Tumor Necrosis Factor (TNF) is a multifunctional cytokine with potent pro-inflammatory effects, and is implicated in many inflammatory and autoimmune diseases. Cytokines such as interleukin I (IL1) and TNF are key mediators of the inflammation which induces bone and joint destruction in RA.
Several Single nucleotide polymorphisms (SNPs) have been identified in the TNFα gene. SNPs within the coding region of cytokine genes tend to be silent while those in promoter region have been associated with differential expression of cytokines as well as severity or susceptibility to various diseases.
The promoter polymorphisms at TNF gene have been associated with disease susceptibility, or severity of joint damage and auto antibody production in RA in different populations.
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In our study, we investigated the possible association between LTA252A>G, TNFα-308G>A and TNFα-1031T>C polymorphisms with susceptibility, activity and severity of RA.
We conducted our study on 35 rheumatoid arthritis cases compared to 35 age and sex matched healthy unrelated controls for analysis of TNFα- 308, TNFα- 1031& LTA 252 gene polymorphism by PCR-RFLP method.
Regarding disease susceptibility, the frequency of the wild type (GG) was significantly higher in RA patients (85.7%) compared to mutant types (14.3%) and mutant types (AG, AA) were significantly higher in controls (45.7%) compared to RA patients (14.3%) (p=0.004).
In the present study, regarding TNFα-1031T>C polymorphism the mutant types (TC & CC) were less frequently represented among RA patients (31.5%) compared to controls (40.0%). The difference was not statistically significant (p=0.454).
In the current study, LTA 252 A>G genotype distribution was similar between patients and controls (AA 42.9%vs51.4%; AG 51.4% vs 45.7%, GG 5.7% vs 2.9%, and AG+GG 57.1% vs 48.6 respectively).
We investigated the influence of TNF-α 308 G/A polymorphism genotypes on disease activity (represented by DAS28) and we observed that the patients who were in remission showed only one patient (100%) with AA genotype, while there were no patients in remission carrying GA or GG genotypes. On the other hand, patients with no disease remission had more frequently wild (GG) genotype (88.2%) compared to AG (8.9%) and AA (2.9%). So, There was a highly statistically significant association between wild type (GG) and disease activity which represented by DAS28 (p=0.000).
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But, no statistically significant association was found between TNFα-1031T>C polymorphism and LTA 252 A/G polymorphism and whether patients were in remission or not (represented by DAS28).
Regarding disease severity represented by Sharp Score, the heterozygous mutant (AG) genotype of TNFα-308 G>A was more frequently represented among RA patients with a mean value of 80.00 ± 10.00. On the other hand, the wild type (GG) and the homozygous mutant type (AA) were less frequently represented among RA patients with a mean value of 34.13 ± 24.24 and 21.00 ± 12.72 respectively. There was a statistically significant difference between wild type (GG), heterozygous mutant type (AG) and homozygous mutant type (AA) (p= 0.007).
However, we did not find any statistically significant association regarding disease severity represented by Sharp Score in RA patients and TNFα-1031T>C polymorphism or LTA 252 A/G polymorphism.