Analysis of the promoter regions of disease-causing genes in maturity-onset diabetes of the young patients
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Аутори
Komazec, JovanaRistivojević, Bojan
Zukić, Branka
Zdravković, Vera
Karan-Đurašević, Teodora
Pavlović, Sonja
Ugrin, Milena
Чланак у часопису (Објављена верзија)
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Приказ свих података о документуАпстракт
Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes caused by the variants in MODY-related genes. In addition to coding variants, variants in the promoter region of MODY-related genes can cause the disease as well. In this study, we screened the promoter regions of the most common MODY-related genesGCK,HNF1A,HNF4AandHNF1Bin our cohort of 29 MODY patients. We identified one genetic variant in theHNF1Agene, a 7 bp insertion c.-154-160insTGGGGGT, and three variants in theGCKgene, -282C gt T; -194A gt G; 402C gt G appearing as set. Chloramphenicol acetyltransferase (CAT) assay was performed to test the effect of the 7 bp insertion and the variant set on the activity of the reporter gene in HepG2 and RIN-5F cell, respectively, where a decreasing trend was observed for both variants. In silico analysis and electrophoretic mobility shift assay showed that the 7 bp insertion did not create the binding site for new transcriptional factors, but gave rise to additional bin...ding sites for the existing ones. Results from our study indicated that the 7 bp insertion in theHNF1Agene could be associated with the patient's diabetes. As for theGCKvariant set, it is probably not associated with diabetes in patients, but it may modify the fasting glucose level by causing small elevation in variant set carriers. We have presented two promoter variants in MODY-related genes. Variant in theHNF1Agene is presumed to be disease-causing and theGCKpromoter variant set could be a phenotype modifier.
Кључне речи:
Promoter variants / Maturity-onset diabetes of the young (MODY) / HNF1Agene / GCKgene / Functional analysisИзвор:
Molecular Biology Reports, 2020, 47, 9, 6759-6768Издавач:
- Springer, Dordrecht
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
DOI: 10.1007/s11033-020-05734-7
ISSN: 0301-4851
PubMed: 32860162
WoS: 000563808400002
Scopus: 2-s2.0-85089968107
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Komazec, Jovana AU - Ristivojević, Bojan AU - Zukić, Branka AU - Zdravković, Vera AU - Karan-Đurašević, Teodora AU - Pavlović, Sonja AU - Ugrin, Milena PY - 2020 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1359 AB - Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes caused by the variants in MODY-related genes. In addition to coding variants, variants in the promoter region of MODY-related genes can cause the disease as well. In this study, we screened the promoter regions of the most common MODY-related genesGCK,HNF1A,HNF4AandHNF1Bin our cohort of 29 MODY patients. We identified one genetic variant in theHNF1Agene, a 7 bp insertion c.-154-160insTGGGGGT, and three variants in theGCKgene, -282C gt T; -194A gt G; 402C gt G appearing as set. Chloramphenicol acetyltransferase (CAT) assay was performed to test the effect of the 7 bp insertion and the variant set on the activity of the reporter gene in HepG2 and RIN-5F cell, respectively, where a decreasing trend was observed for both variants. In silico analysis and electrophoretic mobility shift assay showed that the 7 bp insertion did not create the binding site for new transcriptional factors, but gave rise to additional binding sites for the existing ones. Results from our study indicated that the 7 bp insertion in theHNF1Agene could be associated with the patient's diabetes. As for theGCKvariant set, it is probably not associated with diabetes in patients, but it may modify the fasting glucose level by causing small elevation in variant set carriers. We have presented two promoter variants in MODY-related genes. Variant in theHNF1Agene is presumed to be disease-causing and theGCKpromoter variant set could be a phenotype modifier. PB - Springer, Dordrecht T2 - Molecular Biology Reports T1 - Analysis of the promoter regions of disease-causing genes in maturity-onset diabetes of the young patients EP - 6768 IS - 9 SP - 6759 VL - 47 DO - 10.1007/s11033-020-05734-7 ER -
@article{ author = "Komazec, Jovana and Ristivojević, Bojan and Zukić, Branka and Zdravković, Vera and Karan-Đurašević, Teodora and Pavlović, Sonja and Ugrin, Milena", year = "2020", abstract = "Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes caused by the variants in MODY-related genes. In addition to coding variants, variants in the promoter region of MODY-related genes can cause the disease as well. In this study, we screened the promoter regions of the most common MODY-related genesGCK,HNF1A,HNF4AandHNF1Bin our cohort of 29 MODY patients. We identified one genetic variant in theHNF1Agene, a 7 bp insertion c.-154-160insTGGGGGT, and three variants in theGCKgene, -282C gt T; -194A gt G; 402C gt G appearing as set. Chloramphenicol acetyltransferase (CAT) assay was performed to test the effect of the 7 bp insertion and the variant set on the activity of the reporter gene in HepG2 and RIN-5F cell, respectively, where a decreasing trend was observed for both variants. In silico analysis and electrophoretic mobility shift assay showed that the 7 bp insertion did not create the binding site for new transcriptional factors, but gave rise to additional binding sites for the existing ones. Results from our study indicated that the 7 bp insertion in theHNF1Agene could be associated with the patient's diabetes. As for theGCKvariant set, it is probably not associated with diabetes in patients, but it may modify the fasting glucose level by causing small elevation in variant set carriers. We have presented two promoter variants in MODY-related genes. Variant in theHNF1Agene is presumed to be disease-causing and theGCKpromoter variant set could be a phenotype modifier.", publisher = "Springer, Dordrecht", journal = "Molecular Biology Reports", title = "Analysis of the promoter regions of disease-causing genes in maturity-onset diabetes of the young patients", pages = "6768-6759", number = "9", volume = "47", doi = "10.1007/s11033-020-05734-7" }
Komazec, J., Ristivojević, B., Zukić, B., Zdravković, V., Karan-Đurašević, T., Pavlović, S.,& Ugrin, M.. (2020). Analysis of the promoter regions of disease-causing genes in maturity-onset diabetes of the young patients. in Molecular Biology Reports Springer, Dordrecht., 47(9), 6759-6768. https://doi.org/10.1007/s11033-020-05734-7
Komazec J, Ristivojević B, Zukić B, Zdravković V, Karan-Đurašević T, Pavlović S, Ugrin M. Analysis of the promoter regions of disease-causing genes in maturity-onset diabetes of the young patients. in Molecular Biology Reports. 2020;47(9):6759-6768. doi:10.1007/s11033-020-05734-7 .
Komazec, Jovana, Ristivojević, Bojan, Zukić, Branka, Zdravković, Vera, Karan-Đurašević, Teodora, Pavlović, Sonja, Ugrin, Milena, "Analysis of the promoter regions of disease-causing genes in maturity-onset diabetes of the young patients" in Molecular Biology Reports, 47, no. 9 (2020):6759-6768, https://doi.org/10.1007/s11033-020-05734-7 . .