Elsevier

Experimental Neurology

Volume 167, Issue 2, February 2001, Pages 456-459
Experimental Neurology

Brief Communication
Association between Alzheimer's Disease and a Functional Polymorphism in the Myeloperoxidase Gene

https://doi.org/10.1006/exnr.2000.7560Get rights and content

Abstract

A polymorphism in the Myeloperoxidase gene (MPO) has previously been demonstrated to be associated with gender-specific risk in an Alzheimer's Disease (AD) autopsy sample. We have investigated this polymorphism in our own samples of 226 Caucasian cases and 166 controls and 59 Hispanic cases and 75 controls. In Caucasians we find a significant association between MPO genotype and AD (P = 0.03), although we do not observe any effects of gender or any interaction with the APOE gene. Specifically, the MPO GG genotype contributes a 1.57-fold increased risk for AD. In Hispanics there was no effect of MPO genotype, or of MPO genotype in interaction with age or gender, on diagnosis of AD.

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    In addition, we previously found MPO expression in microglia in AD by immunohistochemistry, which was unexpected because MPO expression is thought to be limited to bone marrow myeloid precursors [25]. In epidemiological studies, the higher expressing −463G MPO polymorphism has been associated with increased risk or earlier onset of AD [25,34–38] as well as risk for several types of cancer [39–46,95] suggesting a causative or contributory role for MPO expression in non-myeloid cells in these disease states. The normal function of MPO is to combat invading microbes.

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    The GG homozygote and the G allele increase the risk towards depressive disorder (Gałecki et al. (in press-a)). Interestingly, the GG homozygote also increases the risk of neurodegenerative disorders, such as Alzheimer's disease (Crawford et al., 2001). Catalase (CAT) is - as explained - another antioxidant enzyme participating in the first line defense against free radicals and their derivatives.

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    We also found no association between myeloperoxidase protein expression and genotypes in all individuals and normal controls. Crawford et al. (16) recruited 226 Caucasian Alzheimer's disease patients and 166 controls as well as 59 Hispanic Alzheimer's disease patients and 75 controls to investigate the relationship between myeloperoxidase gene polymorphism and Alzheimer's disease. They found that individuals with myeloperoxidase G/G genotype have a 1.57-fold increased risk to develop Alzheimer's disease in Caucasians; however, there is no association between myeloperoxidase genotype and Alzheimer's disease in Hispanics.

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    An interaction between the presence of APOE4 and that of the −463A allele of MPO was found only in men in a Finnish study (Reynolds et al., 2000). One North American and two European studies (Combarros et al., 2002; Crawford et al., 2001; Leininger-Muller et al., 2003) failed to replicate this genetic interaction, although possible interactions with gender were reported in some studies. In an English population (Robson et al., 2004), neither the transferrin C2 allele, nor the C282Y allele of HFE had any effect alone on AD risk, with ORs close to 1, but the two variants together increased the risk five times (SF = 5.1, p = 0.01).

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1

These authors contributed equally.

2

To whom correspondence and reprint requests should be addressed. E-mail: [email protected].

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