title: Variants of ST8SIA1 are associated with risk of developing multiple sclerosis.
abstract: 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.
authors.affiliation: Institute of Genomic Medicine and Department of Pediatrics, UMDNJ-New Jersey Medical School, Newark, New Jersey, United States of America.
authors.forename: Seema
authors.initials: S
authors.lastname: Husain
authors.forename: Cagri
authors.initials: C
authors.lastname: Yildirim-Toruner
authors.forename: Justin P
authors.initials: JP
authors.lastname: Rubio
authors.forename: Judith
authors.initials: J
authors.lastname: Field
authors.forename: Marvin
authors.initials: M
authors.lastname: Schwalb
authors.forename: Stuart
authors.initials: S
authors.lastname: Cook
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Emilia
authors.initials: E
authors.lastname: Vitale
mesh_terms: D001315:Australia; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012799:Sialyltransferases / Q000235:genetics*
chemical_list: D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase