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Rheumatology Advance Access published online on June 22, 2004
Rheumatology, doi:10.1093/rheumatology/keh281
Rheumatology © British Society for Rheumatology 2004; all rights reserved
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Received March 1, 2004
Accepted May 19, 2004

Original Papers

VEGF gene polymorphisms and susceptibility to rheumatoid arthritis

S. W. Han 1, G. W. Kim 1, J. S. Seo 1, S. J. Kim 1, K. H. Sa 1, J. Y. Park 1, J. Lee 2, S. Y. Kim 3, J. J. Goronzy 4, C. M. Weyand 4, Y. M. Kang 1*

1 Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
2 Diagnostic Radiology, Kyungpook National University School of Medicine, Daegu, Republic of Korea
3 Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu, Republic of Korea
4 Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: ymkang{at}knu.ac.kr.


  Abstract

Objectives. To investigate polymorphisms of the VEGF gene in patients with rheumatoid arthritis (RA), their relationship to clinical features and the radiographic progression of joint disease.

Methods. One hundred and forty patients with RA and 149 healthy unrelated controls were recruited. We examined four polymorphisms of the VEGF gene which are reported to be associated with production of vascular endothelial growth factor (VEGF), using polymerase chain reaction (PCR) restriction fragment length polymorphism assay and amplification refractory mutation system (ARMS) PCR. Haplotypes were predicted by Bayesian algorithm using the Phase program.

Results. All four polymorphisms were in Hardy-Weinberg equilibrium in both patients and controls. The frequency of the 936 T allele, which has been associated with lower production of VEGF, was significantly increased in RA patients compared with controls (22.7 vs 13.4%, P = 0.002). The frequencies of two haplotypes (CGCT and AAGT) which were predicted using the Phase program were significantly increased in RA patients compared with controls [33 vs 14%, odds ratio (OR) 2.636, 95% confidence interval (CI) 1.38-5.04 for CGCT; 17 vs 6%, OR 3.08, 95% CI 1.20-7.92 for AAGT]. The carriers of the susceptible haplotypes in RA patients had a younger age at disease onset but did not show a difference in the progression rate of radiographic joint destruction.

Conclusions. Our data suggest that the VEGF gene may play a role in the development of RA

Keywords: Vascular endothelial growth factor; Rheumatoid arthritis; Polymorphism
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