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Rheumatology Advance Access originally published online on July 11, 2006
Rheumatology 2007 46(2):220-226; doi:10.1093/rheumatology/kel210
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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
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p21 gene polymorphisms in systemic lupus erythematosus

E. K.-P. Kong, W.-P. Chong, W. H.-S. Wong, C.-S. Lau1, T.-M. Chan1, P. K.-M. Ng2, Y.-Q. Song2, W. Mak2 and Y.-L. Lau

Department of Paediatrics and Adolescent Medicine, 1Department of Medicine and 2Department of Genome Research Centre, The Hong Kong Jockey Club Research Center, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

Correspondence to: Yu-Lung Lau, MD, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. E-mail: lauylung{at}hkucc.hku.hk


   Abstract

Objective. Cyclin-dependent kinase inhibitor 1A (p21) is a negative regulator in the cell cycle. Development of sex-linked lupus-like syndrome in p21–/– mice and reduced p21 gene expression in patients with systemic lupus erythematosus (SLE) compared with those in healthy controls suggested that p21 is a susceptibility gene of SLE. We investigated the same by a case-control association study.

Methods. Six single nucleotide polymorphisms, p21US G/A, p21DS C/A, p21-1022 G/A, p21C31 C/A, p21In2 G/C and p21UTR T/C, were genotyped in 516 SLE patients and 693 healthy controls. Association of genotypes and alleles with disease, disease phenotypes, haplotypes construction, linkage disequilibrium analysis and p21 mRNA expression were performed.

Results. We found a significant association of p21US A allele (OR = 0.23, 95% CI: 0.14–0.38, P < 0.001) and p21-1022 A allele (OR = 1.95, 95% CI: 1.37–2.78, P < 0.001) with SLE. We identified significant differences in the frequencies of haplotypes ht1-ACACCC, which contains p21US A allele, and ht2-GCACCC, which contains p21-1022 A allele, between SLE patients and controls (P < 0.0001). Besides, the p21US GA was associated with SLE patients suffering from arthritis (P = 0.003). We also observed differential p21 mRNA expressions among different genotypes of p21US and p21-1022 which were statistically significant.

Conclusion. Our results suggested that the p21US A allele and p21-1022 A allele were both associated with the development of SLE, and the p21US A allele was associated with arthritis in SLE patients.

KEY WORDS: SLE, p21, Susceptibility, Single nucleotide polymorphism, Haplotype

Submitted 3 March 2006; revised version accepted 11 May 2006.
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