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Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in gulf war veterans


  • Georgirene D. Vladutiu PhD,

    Corresponding author
    1. Departments of Pediatrics, Neurology, and Pathology, School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York
    • Division of Genetics, Department of Pediatrics, University at Buffalo, The State University of New York, 936 Delaware Avenue, Buffalo, NY 14209
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  • Benjamin H. Natelson MD

    1. War-Related Illness and Injury Study Center, VA Medical Center, and CFS Cooperative Research Center, UMDNJ-New Jersey Medical School, East Orange, New Jersey
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Genes associated with muscle metabolism and physical endurance were evaluated for variants that may contribute to the etiology of medically unexplained severe and chronic fatigue. Subjects included 49 Gulf War veterans and 61 nonveterans with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) and 30 veterans and 45 nonveterans who served as healthy controls. Increased risk for CFS/ICF was associated with alterations of the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene within the Gulf War veteran sample only. The I allele frequency was decreased in affected versus unaffected veterans (0.15 versus 0.48; odds ratio [OR], 5.08; 95% confidence interval [CI], 1.97–13.35; P < 0.0001). Correspondingly, the II genotype was decreased fourfold in affected veterans (0.08 versus 0.35; OR = 5.87; 95% CI: 1.21–28.36; P = 0.02), and the DD genotype was increased twofold (0.78 versus 0.39; OR, 5.4; 95% CI, 1.6–18.4; P = 0.007). Veterans with the DD genotype were eight times more likely to develop CFS/ICF than were those with the II genotype (OR, 8.30; 95% CI, 1.50–56.09; P = 0.009). Muscle Nerve 30: 38–43, 2004