SALT LAKE CITY—ST8SIA1 is a susceptibility gene for multiple sclerosis (MS) and is transmitted primarily paternally, according to research presented at the 133rd Annual Meeting of the American Neurological Association. The finding may lead to new approaches for understanding the molecular pathophysiology of MS, reported Seema Husain, PhD, Research Associate at the Institute of Genomic Medicine, University of Medicine and Dentistry of New Jersey in Newark, and colleagues.
Two independent studies involving single-nucleotide polymorphism (SNP) analysis and gene sequence were conducted. The allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12, was first found in a single three-generation Pennsylvania Dutch family, in which the rs4762896 SNP was segregated along with the HLA DR15/DQ6 haplotype in patients with MS. Similar observations were made in a study of 274 Australian family trios that had an affected child and unaffected parents. Within this sample, researchers reported evidence of transmission disequilibrium of the paternal alleles for three more SNPs—rs704219, rs2041906, and rs1558793.
In the Pennsylvania Dutch family, six members were diagnosed with clinically definite MS and one had clinically probable MS. The investigators found only rs4762896 segregate along with the HLA DR15/DQ6 haplotype in the seven affected individuals.
An examination of the Australian sample of 209 trios showed significantly increased transmission of paternal alleles for rs704219, rs2041906, and rs1558793. An additional 65 trios from Tasmania were also genotyped for these three SNPs, and the same trend was observed.
In an analysis of interaction between the SNPs typed in the extended Australian cohorts (rs704219, rs2041906, and rs1558793) and HLA DR15/DQ6, the trios were divided into DR15-positive (n = 145) and DR15-negative (n = 128) groups. Transmission disequilibrium test analysis was completed separately. Results were similar but less significant than those in the previous analysis. In addition, the Australian cohort partially shared one haplotype with the Pennsylvania Dutch family—the T allele of rs1558793 and the A allele of rs2041906.
“Our results suggest that ST8SIA1 may be an MS susceptibility gene possibly regulated by genomic imprinting,” said Dr. Husain and colleagues. “Outside of the immunoregulatory system, this is the first gene extensively involved in neuronal function and membrane structure to be implicated with MS.”
—Laura Sassano