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A
Dinucleotide Deletion in CD24 Confers Protection against Autoimmune
Diseases.
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.
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.
PMID:
17411341 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17411341&itool=pubmed_DocSum |
