Analysis of the promoter regions of disease-causing genes in maturity-onset diabetes of the young patients.
Mol Biol Rep
; 47(9): 6759-6768, 2020 Sep.
Article
en En
| MEDLINE
| ID: mdl-32860162
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 genes GCK, HNF1A, HNF4A and HNF1B in our cohort of 29 MODY patients. We identified one genetic variant in the HNF1A gene, a 7 bp insertion c.-154-160insTGGGGGT, and three variants in the GCK gene, -282C>T; -194A>G; 402C>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 the HNF1A gene could be associated with the patient's diabetes. As for the GCK variant 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 the HNF1A gene is presumed to be disease-causing and the GCK promoter variant set could be a phenotype modifier.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
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Factor Nuclear 1-alfa del Hepatocito
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Quinasas del Centro Germinal
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Biol Rep
Año:
2020
Tipo del documento:
Article