A dinucleotide deletion in CD24 confers protection against autoimmune diseases

Lizhong Wang, Shili Lin, Kottil W. Rammohan, Zhenqiu Liu, Jin Qing Liu, Run Hua Liu, Nikki Guinther, Judy Lima, Qunmin Zhou, Tony Wang, Xincheng Zheng, Dan J. Birmingham, Brad H. Rovin, Lee A. Hebert, Yeeling Wu, D. Joanne Lynn, Glenn Cooke, C. Yung Yu, Pan Zheng, Yang Liu

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

It is generally believed that susceptibility to both organ-specific and systemic autoimmune diseases is under polygenic control. Although multiple genes have been implicated in each type of autoimmune disease, few are known to have a significant impact on both. Here, we investigated the significance of polymorphisms in the human gene CD24 and the susceptibility to multiple sclerosis (MS) and systemic lupus erythematosus (SLE). We used cases/control studies to determine the association between CD24 polymorphism and the risk of MS and SLE. In addition, we also considered transmission disequilibrium tests using family data from two cohorts consisting of a total of 150 pedigrees of MS families and 187 pedigrees of SLE families. Our analyses revealed that a dinucleotide deletion at position 1527 approximately 1528 (P1527(del)) from the CD24 mRNA translation start site is associated with a significantly reduced risk (odds ratio = 0.54 with 95% confidence interval = 0.34-0.82) and delayed progression (p = 0.0188) of MS. Among the SLE cohort, we found a similar reduction of risk with the same polymorphism (odds ratio = 0.38, confidence interval = 0.22-0.62). More importantly, using 150 pedigrees of MS families from two independent cohorts and the TRANSMIT software, we found that the P1527(del) allele was preferentially transmitted to unaffected individuals (p = 0.002). Likewise, an analysis of 187 SLE families revealed the dinucleotide-deleted allele was preferentially transmitted to unaffected individuals (p = 0.002). The mRNA levels for the dinucleotide-deletion allele were 2.5-fold less than that of the wild-type allele. The dinucleotide deletion significantly reduced the stability of CD24 mRNA. Our results demonstrate that a destabilizing dinucleotide deletion in the 3' UTR of CD24 mRNA conveys significant protection against both MS and SLE.

Original languageEnglish (US)
Pages (from-to)508-517
Number of pages10
JournalPLoS genetics
Volume3
Issue number4
DOIs
StatePublished - Apr 2007

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Wang, L., Lin, S., Rammohan, K. W., Liu, Z., Liu, J. Q., Liu, R. H., Guinther, N., Lima, J., Zhou, Q., Wang, T., Zheng, X., Birmingham, D. J., Rovin, B. H., Hebert, L. A., Wu, Y., Lynn, D. J., Cooke, G., Yu, C. Y., Zheng, P., & Liu, Y. (2007). A dinucleotide deletion in CD24 confers protection against autoimmune diseases. PLoS genetics, 3(4), 508-517. https://doi.org/10.1371/journal.pgen.0030049