Contributions
Abstract: P829
Type: Poster
Abstract Category: Clinical aspects of MS - Paediatric MS
Background: Recent evidence suggests an association between secondhand smoke exposure and multiple sclerosis (MS) and a potential interaction between secondhand smoke and human leukocyte antigen (HLA) genes. This gene-environment interaction has not been assessed in children with acute demyelinating syndromes, ADS (30% of whom will be diagnosed with MS, and 70% of whom will remain monophasic).
Methods: We included monophasic, all of whom were observed for a minimum of 2 years following acute demyelination. Parents completed standardized questionnaires regarding their child"s exposure to smoke in the home, classifying the child as exposed or not exposed. Genetic analyses were performed in the MS and monophasic ADS patients using PCR amplification methods to determine the presence of one or more HLA-DRB1*15 alleles. Logistic regression models (covariates of age and sex) compared SHSe associations between MS patients, monophasic patients, and healthy controls. In children with demyelination, n stratified analyses and logistic regression to examined the relationship between SHSe and the presence of at least one HLA-DRB1*15 allele.
Results: SHSe was more commonly reported in children with demyelination (MS and monophasic ADS) compared to controls (OR=2.24; 95%CI 1.08, 4.63), but the relationship with SHSe was not significant when comparing only the MS patients to healthy controls (OR= 1.84; 95%CI 0.86, 3.95). When comparing MS and monophasic ADS patients, SHSe was not an independent risk factor for MS; however, when both SHSe and one or more HLA-DRB1*15 alleles were present, the odds for MS increased threefold (OR=3.2; 95%CI 1.04, 9.79), indicating a positive additive interaction. The presence of HLA-DRB1*15 alleles did not significantly impact the odds for MS in the absence of SHSe (OR=1.68; 95%CI 0.81, 3.45). Similarly, the presence of SHSe did not significantly impact the odds of MS in the absence of HLA-DRB1*15 alleles (OR=1.22; 95%CI 0.55, 2.66).
Conclusion: In the pilot work, we show a possible interaction between exposure to secondhand tobacco smoke and HLA-DRB1*15 alleles in determining pediatric MS risk.
Disclosure: Dr. Arnold reports personal fees for consulting from Acorda, Biogen, Hoffman LaRoche, MedImmune, Mitsubishi, Novartis, Receptos, Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
Dr. Banwell serves as an un-paid advisor on clinical trials for Biogen-IDEC, Novartis, TevaNeuroscience, and Sanofi; and as a central MRI reviewer for Novartis (remunerated).
Abstract: P829
Type: Poster
Abstract Category: Clinical aspects of MS - Paediatric MS
Background: Recent evidence suggests an association between secondhand smoke exposure and multiple sclerosis (MS) and a potential interaction between secondhand smoke and human leukocyte antigen (HLA) genes. This gene-environment interaction has not been assessed in children with acute demyelinating syndromes, ADS (30% of whom will be diagnosed with MS, and 70% of whom will remain monophasic).
Methods: We included monophasic, all of whom were observed for a minimum of 2 years following acute demyelination. Parents completed standardized questionnaires regarding their child"s exposure to smoke in the home, classifying the child as exposed or not exposed. Genetic analyses were performed in the MS and monophasic ADS patients using PCR amplification methods to determine the presence of one or more HLA-DRB1*15 alleles. Logistic regression models (covariates of age and sex) compared SHSe associations between MS patients, monophasic patients, and healthy controls. In children with demyelination, n stratified analyses and logistic regression to examined the relationship between SHSe and the presence of at least one HLA-DRB1*15 allele.
Results: SHSe was more commonly reported in children with demyelination (MS and monophasic ADS) compared to controls (OR=2.24; 95%CI 1.08, 4.63), but the relationship with SHSe was not significant when comparing only the MS patients to healthy controls (OR= 1.84; 95%CI 0.86, 3.95). When comparing MS and monophasic ADS patients, SHSe was not an independent risk factor for MS; however, when both SHSe and one or more HLA-DRB1*15 alleles were present, the odds for MS increased threefold (OR=3.2; 95%CI 1.04, 9.79), indicating a positive additive interaction. The presence of HLA-DRB1*15 alleles did not significantly impact the odds for MS in the absence of SHSe (OR=1.68; 95%CI 0.81, 3.45). Similarly, the presence of SHSe did not significantly impact the odds of MS in the absence of HLA-DRB1*15 alleles (OR=1.22; 95%CI 0.55, 2.66).
Conclusion: In the pilot work, we show a possible interaction between exposure to secondhand tobacco smoke and HLA-DRB1*15 alleles in determining pediatric MS risk.
Disclosure: Dr. Arnold reports personal fees for consulting from Acorda, Biogen, Hoffman LaRoche, MedImmune, Mitsubishi, Novartis, Receptos, Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
Dr. Banwell serves as an un-paid advisor on clinical trials for Biogen-IDEC, Novartis, TevaNeuroscience, and Sanofi; and as a central MRI reviewer for Novartis (remunerated).