Ann Neurol. 2004 Jun;55(6):793-800
Barcellos LF, Begovich AB, Reynolds RL, Caillier SJ, Brassat D, Schmidt
S, Grams SE, Walker K, Steiner LL, Cree BA, Stillman A, Lincoln RR, Pericak-Vance
MA, Haines JL, Erlich HA, Hauser SL, Oksenberg JR.
Department of Neurology, School of Medicine, University of California
at San Francisco.
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.