Contributions
Abstract: 184
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 17 Environmental factors
Background: A three-way interaction between carriage of any human leukocyte antigen (HLA)-DRB1*15 allele, absence of any HLA-A*02 allele, and smoking with regard to multiple sclerosis (MS) risk has been observed. We aimed to investigate this interaction in more detail by taking into consideration the number of HLA-DRB1*15:01 alleles.
Methods: In two Swedish population-based case-control studies (4872 cases, 4508 controls), subjects of Nordic origin with different genotypes and smoking habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals employing logistic regression. The interaction between different genotypes and smoking was evaluated by calculating the attributable proportion due to interaction.
Results: Compared with DRB1*15:01 negative, A*02:01 positive subjects who had never smoked, the odds ratio (OR) of MS was 11.7 (95% CI 9.33-14.6) among smokers who were heterozygotes for DRB1*15:01 without the protective influence of HLA-A*02:01 and 22.2 (95% CI 12.6-39.0) among smokers who were homozygotes for DRB1*15:01 without HLA-A*02:01. The three-way interaction between DRB1*15:01, absence of A*02:01 and smoking with regard to MS risk was more pronounced among DRB1*15:01 homozygotes than among heterozygotes. The analyses were adjusted for age, gender, residential area and other genetic factors located within the HLA complex that have been associated with MS risk in genome-wide association studies.
Conclusions: The magnitude of the interaction between smoking and HLA MS risk genes depends on the number of DRB1*15:01 alleles. Preferences in peptide binding by allelic variants of class II molecules are likely to be critical for the HLA class II influences on MS.
Disclosure: Of conflict of interest and source of funding:
Dr. Hedström and Dr. Strid report no disclosures.
Dr. Kockum received speaker honoraria from Merck Serono and receives research support from the Swedish Brain Foundation and Horizon2020.
Dr. Olsson served on scientific advisory boards for Merck-Serono, Biogen Idec, and SanofiAventis; served as Co-editor of Current Opinion in Immunology; received speaker honoraria from Novartis and Biogen; and receives research support from Bayer Schering, Sanofi-Aventis, Biogen Idec, the Swedish Research Council, EU fp6, EURATools, the Söderberg Foundation, Bibbi and Nils Jensens Foundation, the Montel Williams Foundation, and the Swedish Brain Foundation.
Dr. Alfredsson receives research support from the Swedish Medical Research Council, the and Swedish Council for Health, Working life and Welfare and the Swedish Brain Foundation. The study was supported by grants from the Swedish Medical Research Council; the Swedish Council for Health, Working Life and Welfare, Bibbi and Niels Jensens foundation, Knut and Alice Wallenberg foundation, the Söderberg foundation, the AFA foundation, the Swedish Brain foundation, and Neuro Sweden.
Abstract: 184
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 17 Environmental factors
Background: A three-way interaction between carriage of any human leukocyte antigen (HLA)-DRB1*15 allele, absence of any HLA-A*02 allele, and smoking with regard to multiple sclerosis (MS) risk has been observed. We aimed to investigate this interaction in more detail by taking into consideration the number of HLA-DRB1*15:01 alleles.
Methods: In two Swedish population-based case-control studies (4872 cases, 4508 controls), subjects of Nordic origin with different genotypes and smoking habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals employing logistic regression. The interaction between different genotypes and smoking was evaluated by calculating the attributable proportion due to interaction.
Results: Compared with DRB1*15:01 negative, A*02:01 positive subjects who had never smoked, the odds ratio (OR) of MS was 11.7 (95% CI 9.33-14.6) among smokers who were heterozygotes for DRB1*15:01 without the protective influence of HLA-A*02:01 and 22.2 (95% CI 12.6-39.0) among smokers who were homozygotes for DRB1*15:01 without HLA-A*02:01. The three-way interaction between DRB1*15:01, absence of A*02:01 and smoking with regard to MS risk was more pronounced among DRB1*15:01 homozygotes than among heterozygotes. The analyses were adjusted for age, gender, residential area and other genetic factors located within the HLA complex that have been associated with MS risk in genome-wide association studies.
Conclusions: The magnitude of the interaction between smoking and HLA MS risk genes depends on the number of DRB1*15:01 alleles. Preferences in peptide binding by allelic variants of class II molecules are likely to be critical for the HLA class II influences on MS.
Disclosure: Of conflict of interest and source of funding:
Dr. Hedström and Dr. Strid report no disclosures.
Dr. Kockum received speaker honoraria from Merck Serono and receives research support from the Swedish Brain Foundation and Horizon2020.
Dr. Olsson served on scientific advisory boards for Merck-Serono, Biogen Idec, and SanofiAventis; served as Co-editor of Current Opinion in Immunology; received speaker honoraria from Novartis and Biogen; and receives research support from Bayer Schering, Sanofi-Aventis, Biogen Idec, the Swedish Research Council, EU fp6, EURATools, the Söderberg Foundation, Bibbi and Nils Jensens Foundation, the Montel Williams Foundation, and the Swedish Brain Foundation.
Dr. Alfredsson receives research support from the Swedish Medical Research Council, the and Swedish Council for Health, Working life and Welfare and the Swedish Brain Foundation. The study was supported by grants from the Swedish Medical Research Council; the Swedish Council for Health, Working Life and Welfare, Bibbi and Niels Jensens foundation, Knut and Alice Wallenberg foundation, the Söderberg foundation, the AFA foundation, the Swedish Brain foundation, and Neuro Sweden.