American Journal of Epidemiology Advance Access originally published online on April 26, 2006
American Journal of Epidemiology 2006 163(12):1084-1090; doi:10.1093/aje/kwj146
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Original Contribution |
Myeloperoxidase Polymorphism and Cognitive Decline in Older Adults in the Health, Aging, and Body Composition Study
1 Department of Geriatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR
2 J. Paul Sticht Center on Aging, Wake Forest University Health Sciences, School of Medicine, Winston-Salem, NC
3 Division of Cancer Prevention and Population Science, Roswell Park Cancer Institute, Buffalo, NY
4 Department of Psychiatry, Neurology and Epidemiology, University of California, San Francisco, San Francisco, CA
5 Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN
6 Intramural Research Program, National Institute on Aging, Bethesda, MD
7 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
8 Department of Biostatistics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR
9 Clinical Research Branch, National Institute on Aging, Baltimore, MD
Correspondence to Dr. Sandra K. Pope, Department of Geriatrics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 808, Little Rock, AR 72205 (e-mail: skpope{at}uams.edu).
Myeloperoxidase, an antimicrobial enzyme, produces oxidative free radicals. Rarely found in normal brain tissue, myeloperoxidase has been detected in microglia associated with Alzheimer's disease plaques. The authors examined a G-463A polymorphism in the promoter region of the myeloperoxidase gene (MPO) to determine the relation of MPO variants to cognitive decline over 4 years in a cohort of adults, aged 70–79 years at baseline (1997–1998), recruited from Memphis, Tennessee, and Pittsburgh, Pennsylvania, into the Health, Aging, and Body Composition Study. In this sample, 8% of the participants had the AA, 36.9% the AG, and 55.2% the GG genotype of MPO. The frequency of AA and AG genotypes was higher in Blacks than Whites (11.2% vs. 5.9%, and 44.1% vs. 32.9%, respectively). Multivariate logistic regression analyses showed that, for participants with the MPO AA genotype, cognitive decline was 1.58 (95% confidence interval: 1.07, 2.35) times more likely than for participants with the AG genotype and 1.96 (95% confidence interval: 1.33, 2.88) times more likely than for those with the GG genotype. Interactions between MPO and race, sex, or the apolipoprotein gene were not significant. In this sample, MPO AA, associated with decreased production of myeloperoxidase, was found to be a risk factor for cognitive decline.
cognition; ethnic groups; peroxidase; polymorphism, genetic; prospective studies
Abbreviations: APOE, apolipoprotein E gene; Health ABC, Health, Aging, and Body Composition; MPO, myeloperoxidase gene; 3MS, Modified Mini-Mental State Examination