Fatigue that has no known medical cause, lasts more than six months, produces a substantial decrease of activity and is accompanied by symptoms associated with infection, as well as rheumatological, and neuropsychiatric symptoms, is known as CFS; idiopathic chronic fatigue (ICF) is fatigue without other symptoms or identifiable cause. CFS/ICF sometimes occurs in an almost epidemic fashion, such as in Gulf War veterans, but its cause is unknown. Genetic factors appear to play a role in both Gulf War veterans and civilian populations. Partial defects in one or more genes combined with environmental factors can result in conditions that include fatigue as a prominent feature. Previous studies have shown that mutations in the myoadenylate deaminase gene (AMPD1) and the carnitine palmitoyltransferase II (CPT2) gene can produce pain, stiffness, cramps or fatigue following strenuous exercise, while a genetic variant known as the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme or ACE (DCP1) gene may impact performance and endurance in trained athletes and army recruits.
In this new study, Drs.Georgirene Vladutiu of the State University of New York at Buffalo and Benjamin Natelson of UMDNJ-New Jersey Medical School evaluated DNA from blood samples collected from 49 Gulf War veterans and 61 nonveterans with CFS/IFS and 30 veterans and 45 nonveterans who were healthy. Blood samples were analyzed for mutations in the AMPD1, DCP1, and CPT2 genes. No significant differences were found in variations of the AMPD1 and CPT2 genes in any of the four groups. However, Gulf War veterans with CFS/ICF showed a higher prevalence of the D variant in the DCP1 gene. Veterans with the DD genotype (which has been associated with alcoholism and cardiac disease) were 8 times more likely to develop CFS or ICF than those with the lower prevalence II genotype.
These results suggest that there may be an interaction between these genetic variants and some factor unique to deployment to the Persian Gulf. If they are supported by future research examining veterans of different wars and war zones, it may be that variants of the ACE gene could be a biological marker for increased risk of war-related illness.
Article: "Association of Medically Unexplained Fatigue with ACE Insertion/Deletion Polymorphism in Gulf War Veterans," Georgirene D. Vladutiu, Ph.D. and Benjamin H. Natelson, M.D., Muscle & Nerve; Published Online: May 14, 2004.