Association of the HLA region with multiple sclerosis as confirmed by a genome screen using >10,000 SNPs on DNA chips

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with a complex genetic background. Here, we present a genome screen for association in small scale, employing 11,555 single nucleotide polymorphisms (SNPs) on DNA chips for genotyping 100 MS patients stratified for HLA-DR2+ and 100 controls. More than 500 SNPs revealed significant differences between cases and controls before Bonferroni correction. A fraction of these SNPs was reanalysed in two additional cohorts of patients and controls, using high-throughput genotyping methods. A marker on chromosome 6p21.32 (rs2395182) yielded the highest significance level, validating the established HLA-DR association.

Sex specifically associated promoter polymorphism in multiple sclerosis affects interleukin 4 expression levels

“…This expression difference appears more meaningful since the C allele of this promoter SNP is associated with [14][15][16][17] Informed consent had been obtained from all patients and controls. Research on human genomic material for MS was approved by the ethics commission of the medical faculty of the Ruhr University Bochum, Germany.…”

Mapping candidate non-MHC susceptibility regions to multiple sclerosis

“…This agrees with the evidence of strong association in the MHC class II region between markers G511525 and D6S2444. 36,37 In addition, the analyses predicted at least 38 potential non-MHC susceptibility regions (Figure 1). Of these, 17 regions have been reported in the linkage and/or GAMES studies in five or more different populations, such as chromosomes 7q21, 2,4,7,14,15,20 17q23, 5,9,14 19q13, 2,9,15,20 and 20p12, 4,14,15 and appear to account for several linkage and association reports in each population.…”

Genetic Correlations of Brain Lesion Distribution in Multiple Sclerosis: An Exploratory Study

“…SNPs within the MHC class II region were predominantly selected on the basis of the described linkage disequilibrium with the HLA-DRB1*1501 allele. 28,29 All genetic data bases were accessed in 2006. The SNP rs numbers and gene symbols were actualized on February 9, 2009.…”