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Rheumatology Advance Access originally published online on February 3, 2006
Rheumatology 2006 45(6):711-717; doi:10.1093/rheumatology/kei262
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Poly(ADP-ribose) polymerase (PARP) polymorphisms associated with nephritis and arthritis in systemic lupus erythematosus

J.-W. Hur, Y.-K. Sung, H. D. Shin1, B. L. Park1, H. S. Cheong1 and S.-C. Bae

Department of Internal Medicine, Hospital for Rheumatic Diseases, Hanyang University, Seoul 133-792 and 1 Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 153–803, Republic of Korea.

Correspondence to: S.-C. Bae, Hospital for Rheumatic Diseases, Hanyang University Medical Center, 17 Haengdang-Dong, Seongdong-Gu, Seoul 133-792, Republic of Korea. E-mail: scbae{at}hanyang.ac.kr

Objective. The objective of this study was to confirm whether polymorphisms of the poly(ADP-ribose) polymerase gene (PARP) are associated with genetic susceptibility to systemic lupus erythematosus (SLE) and to investigate the possible association of nephritis and arthritis in SLE with PARP polymorphisms.

Methods. Using direct DNA sequencing in 24 individuals, we identified 44 sequence variants within exons and their flanking regions, including the 1.5-kb promoter region of PARP. Six common polymorphic sites were selected for larger-scale genotyping (in 350 Korean SLE patients and 330 healthy controls), which identified six common haplotypes.

Results. Although no statistically significant association with the risk of SLE was observed, we found that two single-nucleotide polymorphisms (SNPs –1963A -> G and +28077G -> A) were significantly associated with an increased risk of nephritis, and one non-synonymous variant [+40329T -> C(V762A)] was also significantly associated with an increased risk of arthritis, while the –1963A -> G SNP showed a protective effect on arthritis in Korean SLE patients.

Conclusion. Our results demonstrate that PARP polymorphisms are not associated with SLE susceptibility, but that –1963A -> G, +28077G -> A and +40329T -> C(V762A) are significantly associated with nephritis and arthritis in Korean SLE patients.

KEY WORDS: Poly(ADP-ribose) polymerases, Single-nucleotide polymorphism, Systemic lupus erythematosus


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