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.
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.
Authors: Richard A Maki; Michael Holzer; Khatereh Motamedchaboki; Ernst Malle; Eliezer Masliah; Gunther Marsche; Wanda F Reynolds Journal: Free Radic Biol Med Date: 2019-06-06 Impact factor: 7.376
Authors: Richard A Maki; Vladimir A Tyurin; Robert C Lyon; Ronald L Hamilton; Steven T DeKosky; Valerian E Kagan; Wanda F Reynolds Journal: J Biol Chem Date: 2008-12-05 Impact factor: 5.157
Authors: I Manna; P Valentino; A La Russa; F Condino; R Nisticò; M Liguori; A Clodomiro; V Andreoli; D Pirritano; R Cittadella; A Quattrone Journal: J Negat Results Biomed Date: 2006-02-27
Authors: Jordan H Cater; Janet R Kumita; Rafaa Zeineddine Abdallah; Guomao Zhao; Ana Bernardo-Gancedo; Amanda Henry; Wendy Winata; Mengna Chi; Brin S F Grenyer; Michelle L Townsend; Marie Ranson; Catalin S Buhimschi; D Stephen Charnock-Jones; Christopher M Dobson; Mark R Wilson; Irina A Buhimschi; Amy R Wyatt Journal: Proc Natl Acad Sci U S A Date: 2019-03-08 Impact factor: 11.205