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Arch Neurol. 2004 Mar;61(3):341-4.

Increased risk for Alzheimer disease with the interaction of MPO and A2M polymorphisms.

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  • 1Institute of Neurology, University Magna Graecia, Catanzaro, Italy.

Abstract

BACKGROUND:

The genes encoding myeloperoxidase (MPO) and alpha(2)-macroglobulin (A2M) are involved in molecular pathways leading to beta-amyloid deposition. Two polymorphic sites in these genes (MPO-G/A and A2M-Ile/Val) have been associated with Alzheimer disease (AD), but conflicting findings have been reported in populations with different ethnic backgrounds.

OBJECTIVES:

To study the association of MPO-G/A and A2M-Ile/Val polymorphisms with sporadic AD and to investigate the interactions among the MPO, A2M, and apolipoprotein E (APOE) gene polymorphisms in determining the risk of the development of AD.

DESIGN:

Case-control study.

SETTING:

Referral center for AD in Calabria, southern Italy.

PARTICIPANTS:

One hundred forty-eight patients with sporadic AD and 158 healthy control subjects.

RESULTS:

The MPO-G and A2M-Val alleles were found more frequently in cases than in controls, as were the MPO-G/G and A2M-Val/Val genotypes. The odds ratio (OR) for the MPO-G/G genotype was 1.78 (95% confidence interval [CI], 1.13-2.80); for the A2M-Val/Val genotype, 3.81 (95% CI, 1.66-8.75). The presence of MPO-G/G and A2M-Val/Val genotypes synergistically increased the risk of AD (OR, 25.5; 95% CI, 4.65-139.75). Stratification of cases by sex, age at onset of AD, and APOE-epsilon 4 status did not show significant differences in the distribution of MPO or A2M polymorphisms.

CONCLUSIONS:

The MPO and A2M polymorphisms are associated with sporadic AD in southern Italy. Moreover, a genomic interaction between these polymorphisms increases the risk of the development of AD.

PMID:
15023809
DOI:
10.1001/archneur.61.3.341
[PubMed - indexed for MEDLINE]
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