Increased Risk for Alzheimer Disease With the Interaction of MPO and A2M Polymorphisms

Background

The genes encoding myeloperoxidase (MPO) and α₂-macroglobulin (A2M) are involved in molecular pathways leading to β-amyloid deposition. Two polymorphic sites in these genes (MPO-G/AandA2M-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 ofMPO-G/AandA2M-Ile/Valpolymorphisms with sporadic AD and to investigate the interactions among theMPO,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

TheMPO-GandA2M-Valalleles were found more frequently in cases than in controls, as were theMPO-G/GandA2M-Val/Valgenotypes. The odds ratio (OR) for theMPO-G/Ggenotype was 1.78 (95% confidence interval [CI], 1.13-2.80); for theA2M-Val/Valgenotype, 3.81 (95% CI, 1.66-8.75). The presence ofMPO-G/GandA2M-Val/Valgenotypes 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, andAPOE-ϵ4status did not show significant differences in the distribution ofMPOorA2Mpolymorphisms.

Conclusions

TheMPOandA2Mpolymorphisms are associated with sporadic AD in southern Italy. Moreover, a genomic interaction between these polymorphisms increases the risk of the development of AD.