title: Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk.
abstract: BACKGROUND
  The recently described interaction between smoking, human leukocyte antigen (HLA) DRB1*15 and absence of HLA-A*02 with regard to multiple sclerosis (MS) risk shows that the risk conveyed by smoking differs depending on genetic background. We aimed to investigate whether a similar interaction exists between passive smoking and HLA genotype.
  
  
  METHODS
  We used one case-control study with incident cases of MS (736 cases, 1195 controls) and one with prevalent cases (575 cases, 373 controls). Never-smokers with different genotypes and passive smoking status were compared with regard to occurrence of MS, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). The potential interaction between different genotypes and passive smoking was evaluated by calculating the attributable proportion (AP) due to interaction.
  
  
  RESULTS
  An interaction was observed between passive smoking and carriage of HLA-DRB1*15 (AP 0.3, 95% CI 0.02-0.5 in the incident study, and AP 0.4, 95% CI 0.1-0.7 in the prevalent study), as well as between passive smoking and absence of HLA-A*02. Compared with non-smokers without any of these two genetic risk factors, non-exposed subjects with the two risk genotypes displayed an OR of 4.5 (95% CI 3.3-6.1) whereas the same genotype for subjects exposed to passive smoking rendered an OR of 7.7 (95% CI 5.5-10.8).
  
  
  CONCLUSIONS
  The risk of developing MS associated with different HLA genotypes may be influenced by exposure to passive smoking. The finding supports our hypothesis that priming of the immune response in the lungs may subsequently lead to MS in people with a genetic susceptibility to the disease.
authors.affiliation: Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden anna.hedstrom@ki.se.
authors.forename: Anna Karin
authors.initials: AK
authors.lastname: Hedström
authors.affiliation: Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
authors.forename: Izaura Lima
authors.initials: IL
authors.lastname: Bomfim
authors.affiliation: Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.affiliation: Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
authors.forename: Farren
authors.initials: F
authors.lastname: Briggs
authors.affiliation: Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.affiliation: Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Institute of Environmental Medicine, and Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA, Kaiser Permanente Division of Research, Oakland, CA, USA and Neuroimmunology Unit, Karolinska Institutet at Karolinska University Hospital, Solna, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D015789:HLA-A2 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D065840:Protective Factors; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology*; D013548:Sweden / Q000453:epidemiology; D014028:Tobacco Smoke Pollution / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: C524866:HLA-A*02 antigen; D015789:HLA-A2 Antigen; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D014028:Tobacco Smoke Pollution
keywords: HLA genotype; Multiple sclerosis; case-control study; gene-environment interaction; immunology; passive smoking; smoking