Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis.
Genes Immun
; 9(6): 493-500, 2008 Sep.
Article
in En
| MEDLINE
| ID: mdl-18580885
ABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system with a strong genetic component. Variation in the major histocompatibility complex on chromosome 6p21, specifically the HLA-DRB1*15 haplotype, is the strongest genetic factor for MS, yet it is estimated to account for only a portion of risk for the disease. Previous evidence has implicated the nitric oxide synthase gene (NOS2A) encoding inducible NOS on chromosome 17q11 as a potential MS susceptibility gene. To determine whether variation in the NOS2A gene contributes to MS risk, we investigated a total of 50 polymorphisms within or flanking the locus for evidence of association using a comprehensive analytical strategy. A total of 6265 members from 1858 well-characterized MS families were utilized. No evidence for overtransmission of any individual single-nucleotide polymorphism allele or haplotype to the MS-affected individuals was observed. Furthermore, different transmission rates were not observed in either DRB1*15-positive or DRB1*15-negative family subgroups, or when extreme clinical outcomes characterizing disease progression were examined. The very largest study of NOS2A variation in MS, to date, excludes even a modest role for this locus in susceptibility.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Predisposition to Disease
/
Nitric Oxide Synthase Type II
/
Multiple Sclerosis
Type of study:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Language:
En
Journal:
Genes Immun
Journal subject:
ALERGIA E IMUNOLOGIA
/
BIOLOGIA MOLECULAR
Year:
2008
Document type:
Article
Affiliation country:
United States