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Health and Human Services Department of Defense Veterans Affairs Health and Human Services Gulf War Information Department of Defense Gulf War Information Veterans Affairs Gulf War Information Home Home Advanced Search Glossary FAQs Site Map Contact Us
 Research Topics    |    Major Focus Areas
Research Topics
ACCIDENTS & INJURIES
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BRAIN & NERVOUS
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CHEMICAL WARFARE
DIGESTIVE HEALTH
ENVIRONMENTAL & OCCUPATIONAL HEALTH
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Genetic Studies
Project Summary

Title: Butyrylcholinesterase Genetic Variants in Persons with Gulf War Illness
Synopsis: This study attempts to test theories that unexplained illnesses of Gulf War Veterans is a result of nerve damage caused by exposures to nerve agents and the natural occurring enzyme Butyl cholinesterase.
Overall Project Objective: Our goal is to test the hypothesis that some Gulf War illness may be caused by chemical damage to the nerves. If this hypothesis is correct we expect to find a correlation between low levels of butyrylcholinesterase or between genetically abnormal butyrylcholinesterase and Gulf War illness. Butyrylcholinesterase is a scavenger of nerve agents. A person with low levels of this enzyme or with a genetically defective enzyme would be less protected from nerve agents with the result that more of the agent would reach the nerves.
Status/Results to Date: We tested the frequency of butyrylcholinesterase genetic variants in 226 veterans. 74 said they did not have Gulf War illness, 61 said maybe but they did not know, and 91 said they were sick with Gulf War illness. The healthy group had 1 Fluoride, 0 Atypical, and 24 K-variant alleles (18 heterozygotes and 3 homozygous KK). The maybe group had 0 Fluoride, 2 Atypical, and 28 K-variant alleles (26 heterozygotes and 1 KK). The sick group had 5 Atypical, 3 Fluoride, and 40 K-variant alleles (30 heterozygotes and 5 KK). The most common variant of BchE, the K-variant, did not have a statistically significant correlation with Gulf War illness. The rare variants, Atypical and Fluoride, appeared to be present at a higher frequency in sick veterans. The frequency of the Atypical and Fluoride alleles was 1 in 74 for the healthy group, 2 in 61 for the maybe, group and 8 in 91 for the sick group. Thus out of a total of 11 rare BChE alleles, 73% were found in veterans who reported GWI, and 90% in veterans who had symptoms of GWI. This result suggests a strong association between the rare variants of BChE and GWI. However, the results must be confirmed in a larger group before one can have confidence in the significance of these results. Even if studies with larger groups confirm an association between rare genetic variants of BChE and GWI, such a result would account for less than 10% of the total cases of GWI.
Project:DoD-60
Agency:Department Of Defense
Location:University of Nebraska Medical Center
P.I. Name:Oksana Lockridge, Ph. D.
Research Type:Clinical
Research Focus:Chemical Weapons
Focus Category:Genetic Studies
Status:Complete
Study Start Date:September 30,1997
Estimated Completion Date:March 31,1999
Specific Aims: 1. To obtain blood samples from healthy and sick Gulf War veterans; 2. To obtain histories from the subjects detailing their exposures and symptoms; 3. To measure the activity levels and phenotype of butyrylcholinesterase; 4. To determine the genotype of the butyrylcholinesterase; 5.To see if Gulf War Illness correlates with butyrylcholinesterase activity level or genotype.
Methodology: Gulf War veterans were recruited from the Omaha area. In addition, blood samples have been obtained from the VA Medical Center in East Orange, NJ. Histories were obtained by interviewing the subjects. Blood samples were tested for butyrylcholinesterase activity and phenotype with a spectrophotometric assay. The genotype was determined by amplifying the butyrylcholinesterase gene, digesting the amplified DNA and analyzing for characteristic band sizes on agarose gels.
Most Recent Publications:

Boeck AT, Fry DL, Sastre A, Lockridge O. Naturally occurring mutation, Asp70his, in human butyrylcholinesterase. Annals of Clinical Biochemistry, 39(Pt 2):154-6, Mar 2002. Abstract