Dataset Information

NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis.

ABSTRACT: BACKGROUND: A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the NQO1 gene in the risk for MS in the Spanish Caucasian population. METHODS: We analyzed allelic and genotypic frequency of NQO1 rs1800566 in 290 patients with MS and 310 healthy controls, using TaqMan Assays. RESULTS: NQO1 rs1800566 allelic and genotypic frequencies did not differ significantly between MS patients and controls, and were unrelated with age of onset of MS, gender, and clinical type of MS. CONCLUSIONS: Our results indicate that NQO1 rs1800566 does not have an effect on MS disease risk.

SUBMITTER: Agundez JA

PROVIDER: S-EPMC4022329 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis.

Agúndez José A G JA García-Martín Elena E Martínez Carmen C Benito-León Julián J Millán-Pascual Jorge J Calleja Patricia P Díaz-Sánchez María M Pisa Diana D Turpín-Fenoll Laura L Alonso-Navarro Hortensia H Ayuso-Peralta Lucía L Torrecillas Dolores D Plaza-Nieto José Francisco JF Jiménez-Jiménez Félix Javier FJ

BMC neurology 20140423

<h4>Background</h4>A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the ...[more]

PMID: 24755231

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Project description:BackgroundWe previously reported a relationship between air pollutants and increased risk of pediatric-onset multiple sclerosis (POMS). Ozone is an air pollutant that may play a role in multiple sclerosis (MS) pathoetiology. CD86 is the only non-HLA gene associated with POMS for which expression on antigen-presenting cells (APCs) is changed in response to ozone exposure.ObjectivesTo examine the association between county-level ozone and POMS, and the interactions between ozone pollution, CD86, and HLA-DRB1*15, the strongest genetic variant associated with POMS.MethodsCases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. County-level-modeled ozone data were acquired from the CDC's Environmental Tracking Network. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS was assessed by logistic regression. Interactions between tertiles of ozone level and the GG genotype of the rs928264 (G/A) single nucleotide polymorphism (SNP) within CD86, and the presence of DRB1*15:01 (DRB1*15) on odds of POMS were evaluated. Models were adjusted for age, sex, genetic ancestry, and mother's education. Additive interaction was estimated using relative excess risk due to interaction (RERI) and attributable proportions (APs) of disease were calculated.ResultsA total of 334 POMS cases and 565 controls contributed to the analyses. County-level ozone was associated with increased odds of POMS (odds ratio 2.47, 95% confidence interval (CI): 1.69-3.59 and 1.95, 95% CI: 1.32-2.88 for the upper two tertiles, respectively, compared with the lowest tertile). There was a significant additive interaction between high ozone tertiles and presence of DRB1*15, with a RERI of 2.21 (95% CI: 0.83-3.59) and an AP of 0.56 (95% CI: 0.33-0.79). Additive interaction between high ozone tertiles and the CD86 GG genotype was present, with a RERI of 1.60 (95% CI: 0.14-3.06) and an AP of 0.37 (95% CI: 0.001-0.75) compared to the lowest ozone tertile. AP results indicated that approximately half of the POMS risk in subjects can be attributed to the possible interaction between higher county-level ozone carrying either DRB1*15 or the CD86 GG genotype.ConclusionsIn addition to the association between high county-level ozone and POMS, we report evidence for additive interactions between higher county-level ozone and DRB1*15 and the CD86 GG genotype. Identifying gene-environment interactions may provide mechanistic insight of biological processes at play in MS susceptibility. Our work suggests a possible role of APCs for county-level ozone-induced POMS risk.

Dataset Information

NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis.

Publications

NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis.

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