Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis.
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.
Barcellos
Lisa F
LF
Department of Neurology, School of Medicine, University of California at San Francisco, San Francisco, CA 94143-0435, USA.
Begovich
Ann B
AB
Reynolds
Rebecca L
RL
Caillier
Stacy J
SJ
Brassat
David
D
Schmidt
Silke
S
Grams
Sarah E
SE
Walker
Karen
K
Steiner
Lori L
LL
Cree
Bruce A C
BA
Stillman
Althea
A
Lincoln
Robin R
RR
Pericak-Vance
Margaret A
MA
Haines
Jonathan L
JL
Erlich
Henry A
HA
Hauser
Stephen L
SL
Oksenberg
Jorge R
JR
D000328:Adult; D001741:Black or African American; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015802:HLA-DR2 Antigen; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D015802:HLA-DR2 Antigen; D019001:Nitric Oxide Synthase