title: Butyrylcholinesterase genotype and enzyme activity in relation to Gulf War illness: preliminary evidence of gene-exposure interaction from a case-control study of 1991 Gulf War veterans.
abstract: BACKGROUND
  Epidemiologic studies have implicated wartime exposures to acetylcholinesterase (AChE)-inhibiting chemicals as etiologic factors in Gulf War illness (GWI), the multisymptom condition linked to military service in the 1991 Gulf War. It is unclear, however, why some veterans developed GWI while others with similar exposures did not. Genetic variants of the enzyme butyrylcholinesterase (BChE) differ in their capacity for metabolizing AChE-inhibiting chemicals, and may confer differences in biological responses to these compounds. The current study assessed BChE enzyme activity and BChE genotype in 1991 Gulf War veterans to evaluate possible association of this enzyme with GWI.
  
  
  METHODS
  This case-control study evaluated a population-based sample of 304 Gulf War veterans (144 GWI cases, meeting Kansas GWI criteria, and 160 controls). BChE enzyme activity levels and genotype were compared, overall, in GWI cases and controls. Potential differences in risk associated with cholinergic-related exposures in theater were explored using stratified analyses to compare associations between GWI and exposures in BChE genetic and enzyme activity subgroups.
  
  
  RESULTS
  Overall, GWI cases and controls did not differ by mean BChE enzyme activity level or by BChE genotype. However, for the subgroup of Gulf War veterans with less common, generally less active, BChE genotypes (K/K, U/AK, U/A, A/F, AK/F), the association of wartime use of pyridostigmine bromide (PB) with GWI (OR=40.00, p=0.0005) was significantly greater than for veterans with the more common U/U and U/K genotypes (OR=2.68, p=0.0001).
  
  
  CONCLUSIONS
  Study results provide preliminary evidence that military personnel with certain BChE genotypes who used PB during the 1991 Gulf War may have been at particularly high risk for developing GWI. Genetic differences in response to wartime exposures are potentially important factors in GWI etiology and should be further evaluated in conjunction with exposure effects.
authors.affiliation: Veterans Health Research Program, Baylor University Institute of Biomedical Studies, One Bear Place # 97261, Waco, TX 76798, USA. Lea_Steele@baylor.edu.
authors.forename: Lea
authors.initials: L
authors.lastname: Steele
authors.forename: Oksana
authors.initials: O
authors.lastname: Lockridge
authors.forename: Mary M
authors.initials: MM
authors.lastname: Gerkovich
authors.forename: Mary R
authors.initials: MR
authors.lastname: Cook
authors.forename: Antonio
authors.initials: A
authors.lastname: Sastre
mesh_terms: D000328:Adult; D002091:Butyrylcholinesterase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D047830:Gulf War; D006801:Humans; D008297:Male; D008875:Middle Aged; D008889:Military Personnel; D018923:Persian Gulf Syndrome / Q000139:chemically induced / Q000235:genetics*; D011729:Pyridostigmine Bromide / Q000633:toxicity*; D014728:Veterans
chemical_list: D002091:Butyrylcholinesterase; D011729:Pyridostigmine Bromide