Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis

• Published in: Annals of neurology Vol. 55; no. 6; pp. 793 - 800
• Main Authors: Barcellos, Lisa F., Begovich, Ann B., Reynolds, Rebecca L., Caillier, Stacy J., Brassat, David, Schmidt, Silke, Grams, Sarah E., Walker, Karen, Steiner, Lori L., Cree, Bruce A. C., Stillman, Althea, Lincoln, Robin R., Pericak-Vance, Margaret A., Haines, Jonathan L., Erlich, Henry A., Hauser, Stephen L., Oksenberg, Jorge R.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2004; Willey-Liss
• Subjects: Adult; African Americans; Biological and medical sciences; Case-Control Studies; Chromosomes, Human, Pair 17; Exons - genetics; Family Health; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Haplotypes; HLA-DR2 Antigen; Humans; Linkage Disequilibrium; Male; Medical sciences; Multiple Sclerosis - epidemiology; Multiple Sclerosis - genetics; Neurology; Nitric Oxide Synthase - genetics; Polymorphism, Single Nucleotide; Multiple sclerosis; Nervous system diseases; Central nervous system disease; Genetic linkage; Genetics; Chromosome; Locus; Inflammatory disease
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.20092

A large body of research supports a multifactorial cause in multiple sclerosis (MS), with an underlying genetic susceptibility likely acting in concert with undefined environmental exposures. Here, we used a highly efficient multilocus genotyping assay to study single nucleotide polymorphisms representing variation in 34 genes from inflammatory pathways in a well‐characterized MS familial data set. Evidence of transmission distortion was present for several polymorphisms. Results for the NOS2A locus (exon 10 C/T, D346D) on chromosome 17q11 remained significant after correction for multiple testing and were reproduced in a second independent African American MS data set. In addition, linkage to a NOS2A promoter region polymorphism, (CCTTT)n, was present in a third data set of multicase MS families. Our results provide strong evidence for linkage and association to a new candidate disease gene on chromosome 17q11 in MS and suggest that variation within NOS2A or a nearby locus contributes to disease susceptibility. Ann Neurol 2004