Myeloperoxidase polymorphism and cognitive decline in older adults in the Health, Aging, and Body Composition Study
Sandra K Pope1, Stephen B Kritchevsky, Christine Ambrosone
1Department of Geriatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. skpope@uams.edu
Abstract:
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.
Insights
The myeloperoxidase (MPO) AA genotype, linked to lower enzyme production, was associated with increased cognitive decline in older adults. This MPO variant poses a risk factor for cognitive impairment over four years.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Myeloperoxidase (MPO), an antimicrobial enzyme, generates oxidative free radicals.
- MPO is found in microglia near Alzheimer's disease plaques, suggesting a role in neuroinflammation.
- MPO gene variants may influence susceptibility to cognitive decline.
Purpose of the Study:
- To investigate the association between a G-463A polymorphism in the myeloperoxidase (MPO) gene promoter and cognitive decline.
- To determine if MPO gene variants are risk factors for cognitive decline in older adults.
Main Methods:
- Examined the G-463A polymorphism in the MPO gene promoter in a cohort of adults aged 70-79.
- Utilized multivariate logistic regression to analyze the relationship between MPO genotypes (AA, AG, GG) and cognitive decline over 4 years.
- Assessed genotype frequencies across racial groups (Blacks vs. Whites).
Main Results:
- The MPO AA genotype was significantly associated with an increased likelihood of cognitive decline (1.58 times for AG, 1.96 times for GG).
- MPO genotype frequencies differed between Black and White participants.
- No significant interactions were found between MPO genotype and race, sex, or apolipoprotein gene.
Conclusions:
- The MPO AA genotype, linked to reduced myeloperoxidase production, is a risk factor for cognitive decline in older adults.
- MPO gene variations may play a role in the pathogenesis of age-related cognitive impairment.
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