Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis
| Autor: | D. A. S. Compston, J. L. Haines, Lisa F. Barcellos, Stephen L. Hauser, Margaret A. Pericak-Vance, Patricia P. Ramsay, Stacy J. Caillier, Jorge R. Oksenberg, Silke Schmidt, Stephen Sawcer, Pablo Gabatto |
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| Rok vydání: | 2008 |
| Předmět: |
Multiple Sclerosis
Immunology Nitric Oxide Synthase Type II Locus (genetics) Biology Major histocompatibility complex Polymorphism Single Nucleotide Article Genetic variation Genetics medicine Genetic Predisposition to Disease Allele Gene Genetics (clinical) Polymorphism Genetic Multiple sclerosis Haplotype Case-control study HLA-DR Antigens medicine.disease Case-Control Studies biology.protein HLA-DRB1 Chains |
| Zdroj: | Genes & Immunity. 9:493-500 |
| ISSN: | 1476-5470 1466-4879 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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