Increased Risk for Alzheimer Disease With the Interaction of MPO and A2M Polymorphisms

Zappia, Mario; Manna, Ida; Serra, P.; Cittadella, Rita; Andreoli, Virginia; Russa, Antonella La; Annesi, Fernanda; Spadafora, Patrizia; Romeo, Nelide; Nicoletti, Giuseppe; Messina, Demetrio; Gambardella, Antonio; Quattrone, Aldo

doi:10.1001/archneur.61.3.341

Cited by 48 publications

(32 citation statements)

References 17 publications

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“…Crawford et al [20] reported an increased risk of AD in Caucasians of both sexes carrying the -463 MPO-G/G genotype, but not in Hispanics, and Reynolds et al [21] also found that the -463 MPO-A allele in association with the apoE 4 allele increased the risk of AD only in Finnish men. Combarros et al [19] failed to detect any association between the MPO polymorphism and AD in a Spanish population, whereas Zappia et al [22] found an association between the -463 MPO-G/G genotype and SAD in a southern Italian population. In our Japanese case controls, we failed to detect any association between the MPO polymorphism and SAD.…”

Section: Discussionmentioning

confidence: 94%

No Genetic Association between the Myeloperoxidase Gene –463 Polymorphism and Estrogen Receptor-α Gene Polymorphisms and Japanese Sporadic Alzheimer’s Disease

Usui

Shibata

Ohnuma

et al. 2006

Dement Geriatr Cogn Disord

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Myeloperoxidase (MPO) presence has been demonstrated in microglia associated with senile plaques and contributes to Alzheimer’s disease (AD) pathology through oxidation-induced damage. MPO activity is normally higher in women than in men. Additionally, a functional biallelic (G/A) polymorphism in the promoter region (–463) of the MPO gene has been associated with a gender-specific risk factor for AD, but reports of this association have been inconsistent. Furthermore, estrogen is known to enhance MPO activity in myeloid cells and increases the amount of MPO in plasma. Recently, estrogen replacement therapy has been reported to reduce the risk of developing AD and to help maintain cognitive function in patients with AD. In the current study, we analyzed the MPO –463 polymorphism and two estrogen receptor-α polymorphisms in 205 Japanese sporadic AD patients and 92 controls. The results suggest that there is no significant difference in the genotypic frequencies and allelic frequencies of the MPO –463 polymorphism and the estrogen receptor-α polymorphisms between the Japanese sporadic AD group and the control group.

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Section: Discussionmentioning

confidence: 94%

No Genetic Association between the Myeloperoxidase Gene –463 Polymorphism and Estrogen Receptor-α Gene Polymorphisms and Japanese Sporadic Alzheimer’s Disease

Usui

Shibata

Ohnuma

et al. 2006

Dement Geriatr Cogn Disord

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“…73 In contrast, the A/A genotype was associated with increased risk of squamous cell carcinoma (OR ϭ 1.82, 95% CI ϭ 0.8 -4.1) and adenocarcinoma (OR ϭ 1.36, 95% CI ϭ 0.8 -2.5). 89 No significant association for the MPO genotype and patients with squamous cell carcinoma or adenocarcinoma was observed. 82 There was also no clear evidence of lung cancer risk by histologic types.…”

Section: Mpo G-463a Polymorphism and Lung Cancer Riskmentioning

confidence: 94%

NQO1, MPO, and the risk of lung cancer: A HuGE review

Kiyohara

Yoshimasu

Takayama

et al. 2005

Genetics in Medicine

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The aim of this study is to summarize the available molecular epidemiologic studies of lung cancer and metabolic genes, such as NAD(P)H quinone reductase 1 (NQO1) and myeloperoxidase (MPO). NQO1 plays a dual role in the detoxification and activation of procarcinogens whereas MPO has Phase I activity by converting lipophilic carcinogens into hydrophilic forms. Variant genotypes of both NQO1 Pro187 Ser and MPO G-463A polymorphisms may be related to low enzyme activity. The Pro/Ser and Ser/Ser genotypes combined of NQO1 was significantly associated with decreased risk of lung cancer in Japanese [random effects odds ratio (OR) ϭ 0.70, 95% confidence interval (CI) ϭ 0.56--0.88] among whom the variant allele is common. The variant genotype of MPO was associated with decreased risk of lung cancer among Caucasians (random effects OR ϭ 0.70, 95% CI ϭ 0.47--1.04). Gene-environment interactions in both polymorphisms may be hampered by inaccurate categorization of tobacco exposure. Evidence on gene-gene interactions is extremely limited. As lung cancer is a multifactorial disease, an improved understanding of such interactions may help identify individuals at risk for developing lung cancer. Such a study should include larger sample size and other polymorphisms in the metabolism of tobaccoderived carcinogens and address interactions with smoking status. The effects of polymorphisms are best represented by their haplotypes. In future studies on lung cancer, the development of haplotype-based approaches will facilitate the evaluation of haplotypic effects, either for selected polymorphisms physically close to each other or for multiple genes within the same drug-metabolism pathway. Genet Med 2005:7(7):463-478.Key Words: lung cancer, NAD(P)H quinone oxidoreductase 1 polymorphism, myeloperoxidase polymorphism, molecular epidemiology, meta-analysis GENES NAD(P)H quinone reductase 1 NAD(P)H quinone oxidoreductase 1 (NQO1, EC 1.6.99.2), formerly referred to as DT-diaphorase, is an important flavoprotein that catalyzes the two-electron reduction of carcinogenic quinoid compounds into their reduced form, such as hydroquinones. 1 Benzo(a)pyrene (BP) is one of the most important carcinogens, and the formation of BP quinone-DNA adduct is prevented by NQO1. 2 In contrast, carcinogenic heterocyclic amines present in smoke are metabolically activated by NQO1. 3 Therefore, this enzyme is thought to be involved in both metabolic activation and detoxification of carcinogens. Higher levels of tissue (cytoplasm) expression of the NQO1 have been detected in the lung, kidney, liver, and skeletal muscle, with lower levels in the heart, brain, and placenta. 4 Myeloperoxidase Myeloperoxidase (MPO, EC 1.11.1.7) is a lysosomal hemoprotein located in the azurophilic granules of polymorphonuclear leukocytes and monocytes. MPO is the most abundant protein in neutrophils, constituting approximately 5% of their dry weight. 5 MPO has Phase I metabolizing activity by converting lipophilic carcinogens into hydrophilic forms. 6 Exposure to a variety of pulmon...

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“…These genes were described playing important roles in the immune system of animals (Hayashi et al, 2001;Magnadóttir et al, 2005;Magnadottir, 2010;Zappia et al, 2004). In relevance, a previous study reported that SNPs in A2M is related to the increasing risk for Alzheimer disease in human (Zappia et al, 2004). This suggests that the SNPs identified distributing in the immunerelated genes may play a crucial potential role involving in resistance or susceptibility to invasive pathogens of blunt snout bream.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, the genes, A2M, TLR5 and C3 were found to be contained the highest number of SNPs. These genes were described playing important roles in the immune system of animals (Hayashi et al, 2001;Magnadóttir et al, 2005;Magnadottir, 2010;Zappia et al, 2004). In relevance, a previous study reported that SNPs in A2M is related to the increasing risk for Alzheimer disease in human (Zappia et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

SINGLE NUCLEOTIDE POLYMORPHISMS IDENTIFIED FROM BLUNT SNOUT BREAM (Megalobrama amblycephala) TRANSCRIPTOME THROUGH NEXT GENERATION SEQUENCING

Tran¹,

Gao²,

Zhao³

et al. 2017

PAKJAS

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Single nucleotide polymorphisms (SNPs) are the most dominant type of DNA variations in genome which is useful in genetic linkage mapping and quantitative traits loci analysis. In this study, a SNP's database of blunt snout bream (Megalobrama amblycephala) was obtained from the transcripts of cDNA library using Solexa/Illumina sequencing. A total of 36,326 putative SNPs were discovered from the transcripts. One SNP was found in 29.2 base pair length of the transcripts. The transition and transversion mutation was 21,445 and 12,553 SNPs, respectively. A ratio of transition to transversion was 1.71. Within those yielded SNPs, 10,812 SNPs identified from 2,421 unigenes could be annotated to differential functionality in comparing to public database using BLASTX for gene ontology (GO), eukaryotic orthologous groups of proteins (KOG), and Kyoto encyclopedia of genes and genomes (KEGG). A number of SNPs (n = 7,727, 71.5%) found from 1,628 unigenes were assigned to three main GO categories: 'cellular components', 'molecular function' and 'biology process'. In total, 5,812 SNPs (53.8%) identified from 1,324 unigenes were classified into 25 KOG categories. 4,589 SNPs (42.4%) detected from 975 unigenes were assigned to 278 KEGG pathways. Furthermore, a number of 600 SNPs found from 111 unigenes were successfully annotated in the term 'immune system' via KEGG classification. The SNP's database in this study could be useful for further genetic studies in blunt snout bream.

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Increased Risk for Alzheimer Disease With the Interaction of MPO and A2M Polymorphisms

Abstract: 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.

Cited by 48 publications

References 17 publications

No Genetic Association between the Myeloperoxidase Gene –463 Polymorphism and Estrogen Receptor-α Gene Polymorphisms and Japanese Sporadic Alzheimer’s Disease

No Genetic Association between the Myeloperoxidase Gene –463 Polymorphism and Estrogen Receptor-α Gene Polymorphisms and Japanese Sporadic Alzheimer’s Disease

NQO1, MPO, and the risk of lung cancer: A HuGE review

SINGLE NUCLEOTIDE POLYMORPHISMS IDENTIFIED FROM BLUNT SNOUT BREAM (Megalobrama amblycephala) TRANSCRIPTOME THROUGH NEXT GENERATION SEQUENCING

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