HLA-A Confers an HLA-DRB1 Independent Influence on the Risk of Multiple SclerosisReport as inadecuate




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A recent high-density linkage screen confirmed that the HLA complex contains the strongest genetic factor for the risk of multiple sclerosis MS. In parallel, a linkage disequilibrium analysis using 650 single nucleotide polymorphisms SNP markers of the HLA complex mapped the entire genetic effect to the HLA-DR-DQ subregion, reflected by the well-established risk haplotype HLA-DRB1*15,DQB1*06. Contrary to this, in a cohort of 1,084 MS patients and 1,347 controls, we show that the HLA-A gene confers an HLA-DRB1 independent influence on the risk of MS P = 8.4×10−10. This supports the opposing view, that genes in the HLA class I region indeed exert an additional influence on the risk of MS, and confirms that the class I allele HLA-A*02 is negatively associated with the risk of MS OR = 0.63, P = 7×10−12 not explained by linkage disequilibrium with class II. The combination of HLA-A and HLA-DRB1 alleles, as represented by HLA-A*02 and HLA-DRB1*15, was found to influence the risk of MS 23-fold. These findings imply complex autoimmune mechanisms involving both the regulatory and the effector arms of the immune system in the triggering of MS.



Author: Boel Brynedal , Kristina Duvefelt , Gudrun Jonasdottir, Izaura M. Roos, Eva Åkesson, Juni Palmgren, Jan Hillert

Source: http://plos.srce.hr/



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