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

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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;1528 (P1527del) 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 1 2007

Fingerprint

lupus erythematosus
autoimmune diseases
sclerosis
Systemic Lupus Erythematosus
Autoimmune Diseases
Multiple Sclerosis
allele
Pedigree
Alleles
polymorphism
pedigree
alleles
Odds Ratio
confidence interval
genetic polymorphism
odds ratio
Confidence Intervals
gene
Messenger RNA
disequilibrium

All Science Journal Classification (ASJC) codes

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

Cite this

Wang, L., Lin, S., Rammohan, K. W., Liu, Z., Liu, J. Q., Liu, R. H., ... 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
Wang, Lizhong ; Lin, Shili ; Rammohan, Kottil W. ; Liu, Zhenqiu ; Liu, Jin Qing ; Liu, Run Hua ; Guinther, Nikki ; Lima, Judy ; Zhou, Qunmin ; Wang, Tony ; Zheng, Xincheng ; Birmingham, Dan J. ; Rovin, Brad H. ; Hebert, Lee A. ; Wu, Yeeling ; Lynn, D. Joanne ; Cooke, Glenn ; Yu, C. Yung ; Zheng, Pan ; Liu, Yang. / A dinucleotide deletion in CD24 confers protection against autoimmune diseases. In: PLoS genetics. 2007 ; Vol. 3, No. 4. pp. 508-517.
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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;1528 (P1527del) 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.",
author = "Lizhong Wang and Shili Lin and Rammohan, {Kottil W.} and Zhenqiu Liu and Liu, {Jin Qing} and Liu, {Run Hua} and Nikki Guinther and Judy Lima and Qunmin Zhou and Tony Wang and Xincheng Zheng and Birmingham, {Dan J.} and Rovin, {Brad H.} and Hebert, {Lee A.} and Yeeling Wu and Lynn, {D. Joanne} and Glenn Cooke and Yu, {C. Yung} and Pan Zheng and Yang Liu",
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Wang, L, Lin, S, Rammohan, KW, Liu, Z, Liu, JQ, Liu, RH, Guinther, N, Lima, J, Zhou, Q, Wang, T, Zheng, X, Birmingham, DJ, Rovin, BH, Hebert, LA, Wu, Y, Lynn, DJ, Cooke, G, Yu, CY, Zheng, P & Liu, Y 2007, 'A dinucleotide deletion in CD24 confers protection against autoimmune diseases', PLoS genetics, vol. 3, no. 4, pp. 508-517. https://doi.org/10.1371/journal.pgen.0030049

A dinucleotide deletion in CD24 confers protection against autoimmune diseases. / Wang, Lizhong; Lin, Shili; Rammohan, Kottil W.; Liu, Zhenqiu; Liu, Jin Qing; Liu, Run Hua; Guinther, Nikki; Lima, Judy; Zhou, Qunmin; Wang, Tony; Zheng, Xincheng; Birmingham, Dan J.; Rovin, Brad H.; Hebert, Lee A.; Wu, Yeeling; Lynn, D. Joanne; Cooke, Glenn; Yu, C. Yung; Zheng, Pan; Liu, Yang.

In: PLoS genetics, Vol. 3, No. 4, 01.04.2007, p. 508-517.

Research output: Contribution to journalArticle

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T1 - A dinucleotide deletion in CD24 confers protection against autoimmune diseases

AU - Wang, Lizhong

AU - Lin, Shili

AU - Rammohan, Kottil W.

AU - Liu, Zhenqiu

AU - Liu, Jin Qing

AU - Liu, Run Hua

AU - Guinther, Nikki

AU - Lima, Judy

AU - Zhou, Qunmin

AU - Wang, Tony

AU - Zheng, Xincheng

AU - Birmingham, Dan J.

AU - Rovin, Brad H.

AU - Hebert, Lee A.

AU - Wu, Yeeling

AU - Lynn, D. Joanne

AU - Cooke, Glenn

AU - Yu, C. Yung

AU - Zheng, Pan

AU - Liu, Yang

PY - 2007/4/1

Y1 - 2007/4/1

N2 - 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;1528 (P1527del) 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.

AB - 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;1528 (P1527del) 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.

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