A hypermorphic SP1-binding CD24 variant associates with risk and progression of multiple sclerosis.

Am J Transl Res 2012 29;4(3):347-56. Epub 2012 Jul 29.

A large number of risk alleles have been identified for multiple sclerosis (MS). However, how genetic variations may affect pathogenesis remains largely unknown for most risk alleles. Through direct sequencing of CD24 promoter region, we identified a cluster of 7 new single nucleotide polymorphisms in the CD24 promoter. A hypermorphic haplotype consisting of 3 SNPs was identified through association studies consisting of 935 control and 764 MS patients (P=0.001, odds ratio 1.3). The variant is also associated with more rapid progression of MS (P=0.016, log rank test). In cells that are heterozygous for the risk allele, chromatin immunoprecipitation revealed that risk allele specifically bind to a transcription factor SP1, which is selectively required for the hypermorphic promoter activity of the variant. In MS patients, the CD24 transcript levels associate with the SP1-binding variant in a dose-dependent manner (P=7x10(-4)). Our data revealed a potential role for SP1-mediated transcriptional regulation in MS pathogenesis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426393PMC
October 2012
64 Reads

Publication Analysis

Top Keywords

risk alleles
8
risk allele
8
cd24 promoter
8
multiple sclerosis
8
risk
5
snps identified
4
rank test
4
log rank
4
progression p=0016
4
p=0016 log
4
test cells
4
heterozygous risk
4
chromatin immunoprecipitation
4
immunoprecipitation revealed
4
allele chromatin
4
consisting snps
4
rapid progression
4
cells heterozygous
4
identified association
4
control 764
4

Similar Publications