Radiology - Research Publications

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Start date: 2006 × End date: 2009 × Author: Butzkueven, Helmut ×

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    Variants of ST8SIA1 Are Associated with Risk of Developing Multiple Sclerosis
    Husain, S ; Yildirim-Toruner, C ; Rubio, JP ; Field, J ; Schwalb, M ; Cook, S ; Devoto, M ; Vitale, E ; Reitsma, PH (PUBLIC LIBRARY SCIENCE, 2008-07-09)
    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system of unknown etiology with both genetic and environmental factors playing a role in susceptibility. To date, the HLA DR15/DQ6 haplotype within the major histocompatibility complex on chromosome 6p, is the strongest genetic risk factor associated with MS susceptibility. Additional alleles of IL7 and IL2 have been identified as risk factors for MS with small effect. Here we present two independent studies supporting an allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12 and encoding ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1. The initial association was made in a single three-generation family where a single-nucleotide polymorphism (SNP) rs4762896, was segregating together with HLA DR15/DQ6 in MS patients. A study of 274 family trios (affected child and both unaffected parents) from Australia validated the association of ST8SIA1 in individuals with MS, showing transmission disequilibrium of the paternal alleles for three additional SNPs, namely rs704219, rs2041906, and rs1558793, with p = 0.001, p = 0.01 and p = 0.01 respectively. These findings implicate ST8SIA1 as a possible novel susceptibility gene for MS.
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    Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20
    Bahlo, M ; Booth, DR ; Broadley, SA ; Brown, MA ; Foote, SJ ; Griffiths, LR ; Kilpatrick, TJ ; Lechner-Scott, J ; Moscato, P ; Perreau, VM ; Rubio, JP ; Scott, RJ ; Stankovich, J ; Stewart, GJ ; Taylor, BV ; Wiley, J ; Clarke, G ; Cox, MB ; Csurhes, PA ; Danoy, P ; Drysdale, K ; Field, J ; Foote, SJ ; Greer, JM ; Guru, P ; Hadler, J ; McMorran, BJ ; Jensen, CJ ; Johnson, LJ ; McCallum, R ; Merriman, M ; Merriman, T ; Pryce, K ; Tajouri, L ; Wilkins, EJ ; Browning, BL ; Browning, SR ; Perera, D ; Butzkueven, H ; Carroll, WM ; Chapman, C ; Kermode, AG ; Marriott, M ; Mason, D ; Heard, RN ; Pender, MP ; Slee, M ; Tubridy, N ; Willoughby, E (NATURE PUBLISHING GROUP, 2009-07-01)
    To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).