The association of MPO gene promoter polymorphisms with Alzheimer’s disease risk in Chinese Han population

Abstract

AimThe objective of this study was to explore the genetic association of myeloperoxidase (MPO) gene polymorphisms with risk of Alzheimer's disease (AD).MethodsBlood samples were collected from 116 AD patients and 134 age and gender matched healthy individuals. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to confirm MPO polymorphisms in promoter region. Plasma concentration of MPO was detected by enzyme-linked immuno sorbent assay. Genotype distributions of MPO polymorphisms were compared by χ2 test between the two groups. The status of linkage disequilibrium between MPO two polymorphisms was detected using Haploview. MPO concentrations were analyzed by non-parametric test.ResultsMPO rs2333227 polymorphism was positively associated with AD risk, especially under the AA+GA vs. GG and A vs. G genetic models (P=0.042, OR=1.719, 95%CI=1.017-2.906; P=0.041, OR=1.582, 95%CI=1.016-2.463). While, rs34097845 polymorphism significantly decreased the risk of AD, particularly GA and AA+GA genotypes (P=0.048, OR=0.555, 95%CI=0.308-0.998; P=0.042, OR=0.552, 95%CI=0.310-0.983). In addition, rs2333227 genotypes affected the plasma concentration of MPO. But for rs34097845 polymorphism, only GA genotype exhibited significant association with MPO concentration.ConclusionPolymorphisms in the promoter region of MPO distinctly contribute to AD risk possibly through regulating MPO concentration. Present results should be confirmed by further studies.

Myeloperoxidase Deficiency Inhibits Cognitive Decline in the 5XFAD Mouse Model of Alzheimer’s Disease

“…Furthermore, an interaction was identified between MPO and the APOE ε4 allele, the most common genetic risk factor for late onset AD 41 . Following studies, however, exhibited contradicting findings regarding the association of the 463G/A polymorphism with AD (Crawford et al, 2001; Combarros et al, 2002; Leininger-Muller et al, 2003; Ji and Zhang, 2017). Green et al (2004) have reported elevated MPO immunoreactivity and activity in the cortices of AD patients, along with increased prevalence of its oxidation products.…”

Association of Myeloperoxidase Gene Functional Variant with Schizophrenia and Smoking in a Turkish Population

“…The lysosomal enzyme and peroxidase activity were analyzed in the MPO (23) , which plays a role in the regulation of inflammatory responses, lysosomal pathway, tissue damage, lipid metabolism, and oxidative damage (24) . Not only is MPO activity engaged in the host defense physiology against microorganisms, but also it is involved in the pathophysiology of atherosclerosis, respiratory tract and CNS diseases, and cardiac dysfunction (25) .…”

“…It seems that the genotypes of A/A and MPO -463G/A have a diminished risk of colorectal adenomas, acute leukemia, gastric, lung, and ovarian carcinoma (32) . Ji et al found MPO rs2333227 variant was positively associated with the risk of Alzheimer's disease among the population in China (24) . Galecki et al declared a statistically significant difference in genotype distribution and allele frequency of MPO rs2333227 variants between depressive patients and healthy controls (34) .…”

No association between myeloperoxidase gene rs2333227 G>A polymorphism and Alzheimer's disease risk: a meta-analysis and trial sequential analysis

“…A total of 169 studies were excluded due to duplication, 306 studies were deleted through fulltext review or title and abstract screening, and 12 studies were excluded for other deficiencies. Then, nine publications (10 independent case-control studies) involving 1630 patients and 1630 controls were included to assess the association between MPO rs2333227 G>A polymorphism with AD risk [18,[23][24][25][26][27][28][29][30]. Eight studies were conducted in Caucasian or European populations, and two studies were conducted in Asian populations.…”