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AB0282 Correlations of TGF-β1 (869C/T), CD4- (11743 A/C) and CD4- (10845 A/G) Polymorphism with Biochemical Risk Factor Predict in Rheumatoid Arthritis Patients Progression
  1. Y. Hussien1,
  2. L. Damiati2,
  3. A. Alharbi1,
  4. M. Alghamdi1,
  5. S. Alzahrani1,
  6. A. Elaskari1,
  7. S. Bahlas3
  1. 1Taif University, Taif
  2. 2Stem Cell Unit, King Fahd Medical Research Center
  3. 3King Abdulaziz University, Jeddah, Saudi Arabia

Abstract

Background Rheumatoid arthritis (RA), one of the most common systemic autoimmune diseases, is characterized by chronic joint inflammation and subsequent joint destruction [1]. Transforming growth factor-β1 (TGF-β1) is a member of a family of growth factors. The human CD4 gene maps to chromosome 12p13 in a gene-dense region and its expression are regulated primarily at the transcriptional level [2]. The CD4 enhancer and promoter seem to be the major regulatory regions for CD4 transcription in T cells. Therefore, an analysis of the CD4 enhancer polymorphism can provide insights into regulation of its expression. Clearly, the molecular mechanisms controlling CD4 gene expression are very complex and are controlled by many different signals as the thymocyte develop [3].

Objectives This study will done to recognized the association between TGF-β1 (869C/T), CD4- (11743 A/C) and CD4- (10845 A/G) polymorphism and severity of RA patients.

Methods One hundred fifty female RA patients diagnosed according to the criteria of ACR and 100 healthy female will used as a healthy control group. Genotyping of TGF-β1 (869C/T), CD4-11743 A/C and CD4-10845 A/G were determined by restriction fragment length polymorphism- polymerase chain reaction (PCR-RFLP).

Results The TGF-β1 T allele was associated with susceptibility to RA. Within the RA group, TGF-β1 T allele carriers had a significant increased risk to develop osteoporosis (OR =6.95, 95% CI = -2. 7 – 15.7, P<0.001), as well as more likely to develop bone erosion (OR =1.7, 95% CI =0. 99–2.7, P=0. 034). Better prediction was achieved when the TGF-β1 TT genotype was used in combination with elevated, rheumatoid factor (RF) or C reactive protein (CRP) (OR =6.8, 3.7 respectively). Also, they increased the risk to develop bone erosion in patients with rheumatoid arthritis (OR =3.3, 9.8, P=0.017, 0.001 respectively).Subjects with the CC genotype of CD4-11743 were significantly more likely to develop RA (OR =2.7, P=0.03) and more likely to have severe RA (OR =2.7, P=0.024). Carrier of A allele of CD4-10845 was significantly more likely to develop severe RA (OR =3.7, P=0.000).

Conclusions Our results suggest that TGF-β1 TT genotype may determine the development of osteoporosis and bone erosion in RA. CD4 enhancer gene polymorphisms were associated with susceptibility to RA and may be helpful in early detection of erosive RA.

References

  1. Chang W-W, Su H, He L, Zhao K-F, Wu J-L, Xu Z-W: Association between transforming growth factor-beta1 T869C polymorphism and rheumatoid arthritis: a meta-analysis. Rheumatology (Oxford) 2010, 49:652–6.

  2. Ellmeier W, Sawada S, Littman DR. The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu Rev Immunol 1999;17:523–54.

  3. Jiang H, Peterlin BM. Differential chromatin looping regulates CD4 expression in immature thymocytes. Mol Cell Biol 2008;28:907–12.

Disclosure of Interest None declared

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