A regulatory SNP at position-899 in CDKN1A is associated with systemic lupus erythematosus and lupus nephritis

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The CDKN1A gene encoding a cell cycle inhibitor, p21(WAF1/CIP1), is located in the systemic lupus erythematosus (SLE) susceptibility locus on chromosome 6p21.2. Decreased cellular levels of p21 are associated with SLE. Here, we examine four single-nucleotide polymorphisms (SNPs) within the promoter and two in the first intron of CDKN1A for association with SLE susceptibility. A comparison of 742 Korean SLE patients with 1017 controls disclosed that one SNP (rs762624 C>A at position -899), located at a putative Myb-binding site in the promoter, was associated with SLE susceptibility (P = 0.00047). This association was independent of the SLE-association signal of HLA-DRB1 on 6p21.3, as it was significant after adjustment for SLE-risk DRB1 alleles (P = 0.0012). The same SNP was associated with lupus nephritis (P = 0.000014). The risk allele-carrying promoter sequence displayed similar to 15% lower activity than the non-risk sequence upon fusion to the luciferase gene (P = 0.025). Endogenous CDKN1A mRNA levels measured in Epstein-Barr virus-transformed B cells established from 16 control subjects were linearly correlated with a decreasing copy number of the risk allele (P = 0.024). Accordingly, we conclude that the minor allele A at -899 of CDKN1A is associated with increased susceptibility to SLE and lupus nephritis, and decreased cellular levels of p21. Genes and Immunity (2009) 10, 482-486; doi: 10.1038/gene.2009.5; published online 5 March 2009
Publisher
NATURE PUBLISHING GROUP
Issue Date
2009-07
Language
English
Article Type
Article
Keywords

REVISED CRITERIA; INHIBITOR P21; T-CELLS; IN-VIVO; SUSCEPTIBILITY; CLASSIFICATION; PROLIFERATION; POLYMORPHISMS; ITGAM

Citation

GENES AND IMMUNITY, v.10, no.5, pp.482 - 486

ISSN
1466-4879
DOI
10.1038/gene.2009.5
URI
http://hdl.handle.net/10203/101457
Appears in Collection
BS-Journal Papers(저널논문)
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