
Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population
Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population
Sukhvinder Kaura,⁎, Arif Alib, Yaser Siahbalaeic, Uzair Ahmadc, Fazila Nargisc, A.K. Pandeyd,
Balkirat Singhe
a UGC-PDF, Gene Expression Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
b UGC-BSR-FF, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
c Department of Biosciences, Jamia Millia Islamia, New Delhi, India
d Head, Department of Physiology, ESIC Medical College & Hospital, Faridabad, India
e NC Medical College & Hospital, Panipat, India
A B S T R A C T
Background: Migraine is a common neurovascular disorder affected by various levels of neurotransmitters. Low histamine metabolism is also related with pathophysiology of migraine. As diamine oxidase (DAO) gene variants are linked with higher levels of histamine in migraine patients, we investigated the possible relationship of two variants rs2052129 and rs10156191of this gene with migraine risk in North Indian population.
Methods: A case-control study for 250 migraine patients and 250 matched healthy controls was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results: We found statistically significant differences in allelic frequencies of rs2052129 (p = .009, OR = 1.462; 95% CI: 1.098–1.947) and rs10156191 (p = .019, OR = 1.430; 95% CI: 1.060–1.928) variants in DAO gene. For rs1015691, we were able to show statistically significant association at all genotypic, dominant and allelic levels in both MA (for T allele, p = .020; OR = 1.662, 95% CI: 1.083–2.551) as well as in female subgroup (for T allele, p = .025, OR = 1.460; 95% CI: 1.049–2.033). But no such significant association was found in clinical sub grouping of migraine in rs2052129 as p > .05. However in gender analysis, protective effect of T allele in male migraine patients for rs2052129 (OR < 1) was found.
Conclusions: Our findings clearly indicated that female patient with rs10156191T allele and in MA subgroup showed an increased risk for migraine. Our data also indicated that rs2052129T variant showed a significant role in migraine susceptibility of this population.
Conformational Design and Characterisation of a Truncated Diamine Oxidase from Arthrobacter globiformis
Conformational Design and Characterisation of a Truncated Diamine Oxidase from Arthrobacter globiformis
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Abstract
A functional mini protein can be developed by miniaturising its size. The minimisation technique provides an excellent model system for studying native enzymes, especially in creating an alternative novel biocatalyst. Miniaturised proteins may have enhanced stability, a crucial characteristic for large-scale production and industrial applications. In this study, a huge enzyme molecule, known as diamine oxidase (DAO, comprising 700 amino acids), was selected to undergo the process.
Methods
Results
Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia
Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia
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Sci Rep. 2018 Apr 20;8(1):6342. doi: 10.1038/s41598-018-24652-0.
Author information
- 1
- Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria.
- 2
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
- 3
- Department of Obstetrics and Gynaecology, Division of General Gynaecology and Gynaecologic Oncology, Medical University of Vienna, Vienna, Austria.
- 4
- Forensic Toxicology, Clinical Institute of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
- 5
- Children’s Cancer Research Institute, Vienna, Austria.
- 6
- Section for Medical Statistics (IMS), Center of Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
- 7
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
- 8
- Gynmed Clinic, Vienna, Austria.
- 9
- Division of Maternal and Fetal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States.
- 10
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. thomas.boehm@meduniwien.ac.at.
- 11
- Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria. juergen.pollheimer@meduniwien.ac.at.
Abstract
Human extravillous trophoblast (EVT) invasion of the pregnant uterus constitutes a pivotal event for the establishment of the maternal-fetal interface. Compromised EVT function manifesting in inadequate arterial remodeling is associated with the severe pregnancy disorder early-onset preeclampsia (eoPE).
Recent studies suggest that EVTs invade the entire uterine vasculature including arteries, veins and lymphatics in the first trimester of pregnancy. We therefore hypothesized that EVT-derived factors accumulate in the circulation of pregnant women early in gestation and may serve to predict eoPE.
In contrast to published literature, we demonstrate that placenta-associated diamine oxidase(DAO) is not expressed by maternal decidual cells but solely by EVTs, especially when in close proximity to decidual vessels.
Cultures of primary EVTs express and secret large amounts of bioactive DAO.
ELISA measurements indicate a pregnancy-specific rise in maternal DAO plasma levels around gestational week (GW) 7 coinciding with vascular invasion of EVTs.
Strikingly, DAO levels from eoPE cases were significantly lower (40%) compared to controls in the first trimester of pregnancy but revealed no difference at mid gestation. Furthermore, DAO-containing pregnancy plasma rapidly inactivates pathophysiologically relevant histamine levels.
This study represents the first proof of concept suggesting EVT-specific signatures as diagnostic targets for the prediction of eoPE.
- PMID: 29679053
- PMCID: PMC5910386
- DOI: 10.1038/s41598-018-24652-0
Mapping of the binding sites of human diamine oxidase (DAO) monoclonal antibodies
Mapping of the binding sites of human diamine oxidase (DAO) monoclonal antibodies
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Author information
- 1 Department of Visceral, Transplant and Thoracic Surgery, Molecular Biology Laboratory, Medical University Innsbruck, Schöpfstraße 41, 6020, Innsbruck, Austria. hubert.schwelberger@i-med.ac.at.
- 2 Department of Visceral, Transplant and Thoracic Surgery, Molecular Biology Laboratory, Medical University Innsbruck, Schöpfstraße 41, 6020, Innsbruck, Austria.
- 3 Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen, Denmark.
Abstract
OBJECTIVE:
Recently we characterized five mouse monoclonal antibodies that allow the specific and sensitive detection of human diamine oxidase (DAO). To understand differences in binding characteristics and recognition of enzyme variants, we mapped the antibody binding sites.
METHODS:
Fragments of human DAO were expressed as glutathione-S-transferase fusion proteins that were used for testing antibody binding on immunoblots. Combined information from species cross-reactivity, sequence comparison and binding site-prediction software were used to localize the epitope recognized by each antibody.
RESULTS:
All five monoclonal DAO antibodies bound to linear epitopes between the N3 and enzymatic domains of the 732 amino acid protein. The binding sites could be mapped onto amino acid regions V262-E278 and P279-R288, respectively, which exhibit considerable sequence variation in mammals explaining the fact that the human DAO antibodies do not cross-react with DAO from other species. The antibodies efficiently bind only denatured human DAO but not the native protein.
CONCLUSIONS:
Characterization of the binding sites of the DAO antibodies revealed that the antibodies bind two adjacent epitopes and exhibit similar binding characteristics and species cross-reactivity. As the epitopes do not overlap any of the amino acid substitutions described for clinically significant DAO gene polymorphisms, our antibodies will also be useful for analyses of the mutant DAO proteins.
KEYWORDS:
Diamine oxidase; Epitope mapping; Histamine metabolism; Monoclonal antibodies; Protein expression
- PMID: 29164268
- PMCID: PMC5807474
- DOI: 10.1007/s00011-017-1118-3

Progress on the deficit of the enzyme DAO
Read the original article in LA VANGUARDIA
New research led by Dr. Ramon Tormo, Chief of Gastroenterology and Nutrition Hospital Chiron Barcelona, attributed migraine to reaffirm deficit DAO enzyme.

Plasma diamine oxidase activity is a useful biomarker for evaluating gastrointestinal tract toxicities during chemotherapy with oral fluorouracil anti-cancer drugs in patients with gastric cancer.
Plasma diamine oxidase activity is a useful biomarker for evaluating gastrointestinal tract toxicities during chemotherapy with oral fluorouracil anti-cancer drugs in patients with gastric cancer.
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Author information
- 1 Department of Surgery, Kochi Medical School, Nankoku, Japan. tsutomun@kochi-u.ac.jp
Abstract
OBJECTIVES:
Diamine oxidase (DAO) is an enzyme that catalyzes oxidation and is highly active in the mature upper villus cells of the intestinal mucosa. This study sought to evaluate plasma DAO activities during adjuvant chemotherapy in patients with gastric cancer.
METHODS:
We investigated 20 patients with gastric cancer who were treated with oral fluorouracil anti-cancer drugs as adjuvant chemotherapy. Plasma DAO activity was measured in all patients before chemotherapy and at 2, 4 and 6 weeks after the start of chemotherapy, and quality of life was evaluated simultaneously.
RESULTS:
The median DAO activity after 4 weeks of chemotherapy was significantly decreased compared to the pre-chemotherapy levels (6.6 vs. 7.5 U/l; p = 0.038). The changes in the rate of DAO activity at 2 and 6 weeks following the start of chemotherapy in patients with gastrointestinal tract toxicity were significantly lower than in those without toxicity (p =0.021 and 0.047, respectively). The patient cohort showed a slightly positive correlation between DAO activity and global health status and a negative correlation between DAO activity and appetite loss.
CONCLUSIONS:
Plasma DAO activities may be useful for monitoring and evaluating gastrointestinal tract toxicities induced by adjuvant chemotherapy with oral fluorouracil in patients with gastric cancer.
Copyright © 2012 S. Karger AG, Basel.
- PMID: 22433290
- DOI: 10.1159/000336799