Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis
- 27 April 2004
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 55 (6), 793-800
- https://doi.org/10.1002/ana.20092
Abstract
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 2004Keywords
This publication has 49 references indexed in Scilit:
- Candidate-gene approaches for studying complex genetic traits: practical considerationsNature Reviews Genetics, 2002
- Linkage of the Human Inducible Nitric Oxide Synthase Gene to Type 1 DiabetesJournal of Clinical Endocrinology & Metabolism, 2001
- Genetic susceptibility to MS: a second stage analysis in Canadian MS familiesneurogenetics, 2001
- A map of human genome sequence variation containing 1.42 million single nucleotide polymorphismsNature, 2001
- A meta-analysis of genomic screens in multiple sclerosisMultiple Sclerosis Journal, 2001
- A Test for Linkage and Association in General Pedigrees: The Pedigree Disequilibrium TestAmerican Journal of Human Genetics, 2000
- The potential role of nitric oxide in multiple sclerosisMultiple Sclerosis Journal, 1998
- Molecular Cloning and Structural Organization of the Human Inducible Nitric Oxide Synthase Gene (NOS2)Biochemical and Biophysical Research Communications, 1996
- Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brainsAnnals of Neurology, 1994
- Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice.JCI Insight, 1994