الفهرس 
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Abstract
Summary
Rheumatoid arthritis (RA) is a chronic progressive autoimmune inflammatory disease of the joints which can result in permanent cartilage and bone damage , substantial disability and other extra-articular comorbidities which imposes a huge burden on individuals and society. Although the exact cause of RA is unknown, there are many risk factors that have been associated with RA. When RA occurs, the immune system mistakenly attacks healthy synovial and connective tissue (Srivastava et al ., 2019).
The pathogenesis of RA is still not very clear. Substantial data have demonstrated that RA is the result of interaction between genetics, abnormal immune responses, and environmental triggers (Vojdani , 2014).
Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease caused by genetic susceptibility, environmental effects, and disorders of innate and adaptive immunity, with evidence of autoantibody production that can result in damage to multiple organ systems and the production of autoreactive T cells and autoantibodies against nuclear, cytoplasmic and cell surface antigens (Lessard et al .,2016).
The VEGF gene encodes the VEGF protein, a potent pro‐angiogenicfactor, which increases vascular permeability, proinflammatory cell transport and inflammation ( Elshabrawy et al.,2015).
The pathophysiology of both RA and SLE involves angiogenesis which can maintain a chronic inflammatory state by transporting immune cells to the site of inflammation and to proliferating inflamed tissue (Liu et al., 2015).
Angiogenesis in RA and SLE is promoted by different proangiogenic factors, including vascular endothelial growth factor (VEGF) (Elshabrawy et al.,2015).
The aim of this study was to determine whether the VEGFA −1154G/A polymorphism is associated with risk of RA or SLE and to detect an association between VEGFA −1154G/A SNP and disease activity in both RA and SLE.
This study was conducted on 50 RA patients diagnosed according to 2010ACR/EULAR classification criteria for Rheumatoid arthritis, 50 patients with SLE diagnosed according to 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus and 50 age and sex matched healthy controls.
All patients included in this study were subjected to full history taking, general examination and local examination and Detection of VEGFA −1154G/A single nucleotide polymorphism by polymerase chain reaction (PCR) method for all patients and controls. RA patients were subjected to complete blood count, CRP, ESR, RF , Anti-ccp , serum urea and creatinine. SLE patients were subjected to complete blood count, CRP,ESR, ANA , Anti-dsDNA, C3 , C4, Complete urine analysis , 24 hours urinary proteins, serum urea and creatinine.
This study demonstrated the following :
There was highly significant difference on comparing VEGF (1154G/A) SNP between RA and Controls and (AA) polymorphism was associated with reduced risk of RA (P<0.001).
The frequency of the A allele was significantly higher in controls compared to RA patients, Hence we postulate that A allele might have protective role against RA (P <0.001).
We investigated the association between VEGF (1154G/A) SNP and disease activity as indicated by DAS.28 score and we found that there was no statistically significant difference (P =0.888) between the patients regarding distribution of genotypes according to their DAS.28 score.
As regards Anti-CCP and RF ,(AA) genotype was higher in RA patients who tested -ve in comparison to patients tested +ve (P= 0.002)& (P= 0 .005). (AA) polymorphism may play a role in RA disease prognosis.
There was no significant difference on comparing VEGF (1154G/A) SNP polymorphism between SLE and Controls (P = 0.922). Although the homozygous mutant genotype (AA) was higher in controls (54%) compared to cases (34%) but the results did not reach statistical significance
Analysis of the VEGFA (1154G/A) SNP revealed that the frequency distribution of the A allele was significantly higher in controls (56%) compared to SLE cases (38%) (P = 0.011) . Thus , we suggest that A allele may play a protective role againts SLE .
Distribution of genotypes according to SLEDAI of SLE cases showed no significant difference (P = 0.922) .
Our results indicated the AA genotype was significantly higher in Patients with negative SLICC than Patients with positive SLICC , so AA genotype in SLE patients may be associated with less sever disease (P= 0 .024). (P= 0 .024).
We detected significant difference on comparing homozygous mutant AA genotype versus wild GG genotype in relation to C4 . AA genotype associated with higher level of c4 (P value = 0.008).
There was no a significant association between the developments of lupus nephritis and VEGF (1154G/A) SNP (P=0.419).
Analysis of the association between different genotypes and clinical parameters revealed thatfever , vasculitis andserositis showed significant difference. AA genotype was higher in patients without fever , vasculitis and serositis, so AA genotype may play a role in clinical presentations of SLE disease (P=0.023), (P=0.004) &(P=0.047) respectively.