Myeloperoxidase G-463A polymorphism and Alzheimer's disease in the ApoEurope study.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Epidemiological and molecular genetic studies have shown the existence of several genes associated with increased risk of AD, the major genetic susceptibility locus coding for apolipoprotein E (apoE). A polymorphism in the myeloperoxidase gene (MPO) has previously been associated with AD susceptibility. However, results in the literature are controversial and seem to be dependent on several factors such as gender, apoE polymorphism or the genetic structure of the population. We investigated MPO G-463A and apoE polymorphism in 265 cases and 246 controls from the ApoEurope Study. In females, we found a significant association between MPO genotype and AD (P=0.034), GG genotype frequency being lower in cases (52.4%) as compared to controls (64.2%). In men, there was no significant effect of MPO polymorphism. No interaction was found between MPO polymorphism and apoE epsilon 4 allele. In conclusion, the G-463A polymorphism of MPO was statistically associated with AD in a gender-specific manner. However, given the low significance of P value we suggest no causal effect of the MPO gene in AD, as also evidenced in a recent meta-analysis. Our results support the hypothesis of a possible linkage disequilibrium between the MPO G-463A gene polymorphism and another functional variant involved in AD.
Leininger-Muller
Brigitte
B
INSERM Unité 525, Centre de Médecine Préventive and Faculté de Pharmacie, Nancy, France.
Hoy
Aline
A
Herbeth
Bernard
B
Pfister
Michèle
M
Serot
Jean Marie
JM
Stavljenic-Rukavina
Marina
M
Massana
Luis
L
Passmore
P
P
Siest
Gérard
G
Visvikis
Sophie
S
D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009195:Peroxidase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D009195:Peroxidase