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


OBJECTIVE
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.


METHODS
Case-control study.


METHODS
Referral center for AD in Calabria, southern Italy.


METHODS
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.
Zappia
Mario
M
Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
Manna
Ida
I
Serra
Paolo
P
Cittadella
Rita
R
Andreoli
Virginia
V
La Russa
Antonella
A
Annesi
Fernanda
F
Spadafora
Patrizia
P
Romeo
Nelide
N
Nicoletti
Giuseppe
G
Messina
Demetrio
D
Gambardella
Antonio
A
Quattrone
Aldo
A
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D007558:Italy; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009195:Peroxidase / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012306:Risk; D014633:Valine / Q000235:genetics; D000511:alpha-Macroglobulins / Q000235:genetics*
D001057:Apolipoproteins E; D000511:alpha-Macroglobulins; D007532:Isoleucine; D009195:Peroxidase; D014633:Valine