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MPO And APOEε4 Polymorphisms Interact To Increase Risk For AD In Finnish Males

W. F. Reynolds, M. Hiltunen, M. Pirskanen, A. Mannermaa, S. Helisalmi, M. Lehtovirta, I. Alafuzoff, and H. Soininen
Published 2000 · Biology

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Background: Myeloperoxidase (MPO) is present in senile plaques and surrounding reactive microglia, but not in normal brain parenchyma. MPO in plaques is highest in APOE ε4 carriers, suggesting a functional interaction. An MPO promoter polymorphism (-463G/A) linked to increased MPO expression has been associated with increased risk of AD. Methods: To further define the possible interaction of MPO and APOE ε4, we examined 127 patients with AD and 174 controls from a genetically homogeneous Finnish population. Results: A significantly higher percentage of male patients with AD carried the MPO A and APOE ε4 alleles relative to men carrying neither allele (p < 0.001; OR, 11.4; 95% CI, 3.6 to 6.7). Male APOE ε4 carriers lacking the MPO A allele had an OR of 3.0 (p = 0.01; 95% CI, 1.3 to 6.9), indicating that MPO A enhances AD risk by 3.8-fold. Age at onset was lower in men carrying the MPO A and APOE ε4 alleles (Kaplan—Meier survival analysis; p = 0.01). Also, the MPO AA genotype was associated with selective mortality in men, but not in women. AA genotypes were absent from 159 male patients with AD and controls, representing the expected 5% to 6% in women and male controls younger than age 20. The -463A creates an estrogen receptor binding site that may contribute to these gender differences. Conclustions: MPO A and APOE ε4 alleles interact to increase the risk of AD in men but not in women in this Finnish cohort.
This paper references
Association of the myeloperoxidase -463G-->a polymorphism with lung cancer risk.
L. Le Marchand (2000)
Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor alpha.
M. Maggiolini (1999)
Tau gene polymorphisms and apolipoprotein E epsilon4 may interact to increase risk for Alzheimer's disease.
L. Lilius (1999)
10.1016/0021-9150(96)05894-7
Inhibition of LDL oxidation and myeloperoxidase dependent tyrosyl radical formation by the selective estrogen receptor modulator raloxifene (LY139481 HCL).
S. Zuckerman (1996)
10.1093/HMG/7.12.1953
Genetic association of an (α2-macroglobulin (Val1000lle) polymorphism and Alzheimer's disease
A. Liao (1998)
10.3109/10715769109088949
Oestrogen-induced enhancement of myeloperoxidase activity in human polymorphonuclear leukocytes--a possible cause of oxidative stress in inflammatory cells.
G. Jansson (1991)
10.3109/13506129908993282
In vitro peroxidase oxidation induces stable dimers of beta-amyloid (1-42) through dityrosine bridge formation.
L. Galeazzi (1999)
Clinical and neuropsychological characteristics in familial and sporadic Alzheimer’s disease: relation to apolipoprotein E polymorphism. Neurology 1996;46:413–419
M Lehtovirta (1996)
10.1182/BLOOD.V90.7.2730.2730_2730_2737
An allelic association implicates myeloperoxidase in the etiology of acute promyelocytic leukemia.
W. Reynolds (1997)
10.1002/(SICI)1096-8652(199904)60:4<312::AID-AJH13>3.0.CO;2-K
Sex difference in myeloperoxidase activity of neutrophils
O. Kabutomori (1999)
10.1074/JBC.271.24.14412
An Alu Element in the Myeloperoxidase Promoter Contains a Composite SP1-Thyroid Hormone-Retinoic Acid Response Element*
F. J. Piedrafita (1996)
10.1016/S0960-0760(99)00057-6
Steroid metabolising enzymes in the determination of brain gender
J. Hutchison (1999)
Activation of microglial cells by beta-amyloid protein and interferon-gamma.
L. Meda (1995)
Determination by PCR-RFLP of apo E genotype in a Japanese population.
K. Tsukamoto (1993)
10.1016/S0165-5728(97)00089-1
Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis
R. Nagra (1997)
10.1016/0304-3940(96)12661-6
Apolipoprotein E is highly susceptible to oxidation by myeloperoxidase, an enzyme present in the brain
C. Jolivalt (1996)
10.1074/JBC.271.38.23080
Molecular Chlorine Generated by the Myeloperoxidase-Hydrogen Peroxide-Chloride System of Phagocytes Converts Low Density Lipoprotein Cholesterol into a Family of Chlorinated Sterols*
S. Hazen (1996)
Substantially reduced risk of cancer of the aerodigestive tract in subjects with variant--463A of the myeloperoxidase gene.
I. Cascorbi (2000)
10.1126/SCIENCE.8346443
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.
E. H. Corder (1993)
New Alzheimer’s therapy
J. Schnabel (1993)
10.1073/PNAS.90.20.9649
Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.
D. Schmechel (1993)
10.1182/BLOOD.V46.6.913.913
Granule enzymes of polymorphonuclear neutrophils: A phylogenetic comparison.
P. Rausch (1975)
10.1046/j.1471-4159.1998.70052212.x
Amyloid‐β Deposition in Alzheimer Transgenic Mice Is Associated with Oxidative Stress
M. Smith (1998)
10.1038/1243
Alpha-2 macroglobulin is genetically associated with Alzheimer disease
D. Blacker (1998)
10.1038/34923
Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils
J. Eiserich (1998)
10.1212/WNL.41.4.479
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
S. S. Mirra (1991)
10.1074/JBC.270.39.22777
Identification of a New Subclass of Alu DNA Repeats Which Can Function as Estrogen Receptor-dependent Transcriptional Enhancers (*)
J. Norris (1995)
10.1006/exnr.1998.6977
Myeloperoxidase Polymorphism Is Associated with Gender Specific Risk for Alzheimer's Disease
W. Reynolds (1999)
10.1073/PNAS.92.18.8229
The consensus sequence of a major Alu subfamily contains a functional retinoic acid response element.
G. Vansant (1995)
Genetic association of an alpha-2 macroglobulin (Val1000lle) polymorphism and Alzheimer’s disease
A Liao (1956)
10.1212/WNL.46.2.413
Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease
M. Lehtovirta (1996)
10.1172/JCI8593
A genetic dichotomy model for the inheritance of Alzheimer's disease and common age-related disorders.
R. Tanzi (1999)
10.1016/S0304-3940(99)00071-3
Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease
A. Papassotiropoulos (1999)
10.1016/S0304-3940(99)00833-2
Tau gene polymorphisms and apolipoprotein E ε4 may interact to increase risk for Alzheimer’s disease
L. Lilius (1999)
10.1126/SCIENCE.8323582
New Alzheimer's therapy suggested.
J. Schnabel (1993)
Myeloperoxidase genetic polymorphism and lung cancer risk.
S. London (1997)
10.1212/WNL.34.7.939
Clinical diagnosis of Alzheimer's disease
G. Mckhann (1984)



This paper is referenced by
10.1021/jm3007245
Evaluation of new scaffolds of myeloperoxidase inhibitors by rational design combined with high-throughput virtual screening.
Iyas Aldib (2012)
10.1038/sj.ejhg.5200702
Serum myeloperoxidase concentration in a healthy population: biological variations, familial resemblance and new genetic polymorphisms
A. Hoy (2001)
10.1016/j.freeradbiomed.2019.05.033
Human myeloperoxidase (hMPO) is expressed in neurons in the substantia nigra in Parkinson's disease and in the hMPO-α-synuclein-A53T mouse model, correlating with increased nitration and aggregation of α-synuclein and exacerbation of motor impairment.
R. Maki (2019)
10.1155/MI/2006/36735
Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease
W. Reynolds (2006)
10.1016/J.FREERADBIOMED.2005.01.018
Role of peroxidases in Parkinson disease: a hypothesis.
J. Everse (2005)
10.1038/sj.gene.6363840
Gender and smoking-related risk reduction of periodontal disease with variant myeloperoxidase alleles
P. Meisel (2002)
10.1146/ANNUREV.PUBLHEALTH.24.100901.141015
Will a healthy lifestyle help prevent Alzheimer's disease?
S. Pope (2003)
10.1016/S0021-9150(02)00041-2
Myeloperoxidase polymorphisms in brain infarction. Association with infarct size and functional outcome.
A. Hoy (2003)
10.1016/J.BBRC.2006.08.119
The human myeloperoxidase gene is regulated by LXR and PPARalpha ligands.
W. Reynolds (2006)
10.1074/jbc.M807731200
Aberrant Expression of Myeloperoxidase in Astrocytes Promotes Phospholipid Oxidation and Memory Deficits in a Mouse Model of Alzheimer Disease*
R. Maki (2009)
10.1016/j.neuint.2006.07.007
Convergence of genes implicated in Alzheimer's disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis
C. Carter (2007)
10.1089/ARS.2009.2538
Myeloperoxidase: molecular mechanisms of action and their relevance to human health and disease.
B. S. van der Veen (2009)
10.1111/j.1471-4159.2004.02868.x
Inhibition of the α‐ketoglutarate dehydrogenase complex by the myeloperoxidase products, hypochlorous acid and mono‐N‐chloramine
T. Jeitner (2005)
10.1007/s11926-014-0428-5
Genetics of ANCA-associated Vasculitides
M. Ugarte-Gil (2014)
10.1007/978-1-4939-2155-3_5
Epistasis in the risk of human neuropsychiatric disease.
S. Williams (2015)
10.1016/j.jash.2015.08.006
Gender-specific protective effect of the -463G>A polymorphism of myeloperoxidase gene against the risk of essential hypertension in Russians.
O. Bushueva (2015)
10.1080/00365510600727603
Relation of myeloperoxidase promoter polymorphism and long‐term hormone replacement therapy to oxidized low‐density lipoprotein autoantibodies in postmenopausal women
R. Mäkelä (2006)
Aspects of endothelial function testing in coronary vascular disease
S. Monnink (2003)
10.1515/CCLM.2002.002
Growing Significance of Myeloperoxidase in Non-infectious Diseases
A. Hoy (2002)
10.1159/000091437
No Genetic Association between the Myeloperoxidase Gene –463 Polymorphism and Estrogen Receptor-α Gene Polymorphisms and Japanese Sporadic Alzheimer’s Disease
C. Usui (2006)
10.1016/j.clinbiochem.2008.01.017
The association of myeloperoxidase promoter polymorphism with carotid atherosclerosis is abolished in patients with type 2 diabetes.
R. Mäkelä (2008)
10.1097/01.gim.0000177530.55043.c1
NQO1, MPO, and the risk of lung cancer: A HuGE review
C. Kiyohara (2005)
10.1097/01.LAB.0000077981.49367.46
Myeloperoxidase Gene Variation as a Determinant of Atherosclerosis Progression in the Abdominal and Thoracic Aorta: An Autopsy Study
R. Mäkelä (2003)
10.1016/j.ejmech.2016.07.053
Novel bis-arylalkylamines as myeloperoxidase inhibitors: Design, synthesis, and structure-activity relationship study.
Iyas Aldib (2016)
10.1016/J.BCMD.2013.10.001
Haptoglobin and myeloperoxidase (- G463A) gene polymorphisms in Brazilian sickle cell patients with and without secondary iron overload.
L. C. Barbosa (2014)
10.1016/S0891-0618(01)00126-0
Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology
Hans-J. Bidmon (2001)
10.1046/j.1365-2141.2003.04602.x
Neutrophil myeloperoxidase activity and the influence of two single‐nucleotide promoter polymorphisms
A. Rutgers (2003)
10.1016/j.prp.2018.05.018
The possible association between the presence of an MPO -463 G > A (rs2333227) polymorphism and cervical cancer risk.
Xiao-qing Shi (2018)
10.1186/1471-2148-8-101
The phylogeny of the mammalian heme peroxidases and the evolution of their diverse functions
N. Loughran (2007)
10.1007/S12603-009-0061-6
GAB2 gene does not modify the risk of Alzheimer’s disease in Spanish APOE 4 carriers
R. Ramírez-Lorca (2009)
10.1007/s13277-013-1017-3
Association of myeloperoxidase with ovarian cancer
D. Castillo-Tong (2013)
10.1016/j.humimm.2014.05.008
Myeloperoxidase gene polymorphism predicts fibrosis severity in women with hepatitis C.
R. F. do Carmo (2014)
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