Identification and functional study of GATA4 gene regulatory variants in type 2 diabetes mellitus.
BMC Endocr Disord
; 21(1): 73, 2021 Apr 17.
Article
in En
| MEDLINE
| ID: mdl-33865372
ABSTRACT
BACKGROUND:
Type 2 diabetes mellitus (T2D) is a common and complex disease. Dysfunction of pancreatic ß cells, which cannot release sufficient insulin, plays a central role in T2D. Genetics plays a critical role in T2D etiology. Transcription factor GATA4 is required for the pancreatic development, and GATA4 gene mutations are implicated in neonatal or childhood-onset diabetes. In this study, we aimed to investigate whether regulatory variants in GATA4 gene may change GATA4 levels, conferring susceptibility to T2D development.METHODS:
The promoter region of GATA4 gene was analyzed by targeted sequencing in T2D patients (n = 255) and ethnic-matched controls (n = 371). Dual luciferase activity assay was used for functional study, and EMSA (electrophoretic mobility shift assay) was performed for detecting transcription factor binding.RESULTS:
Thirteen regulatory variants including 5 SNPs were identified. A novel heterozygous variant (32124C > T) and one SNP [31487C > G (rs1053351749)] were only identified in T2D. Both regulatory variants significantly affected GATA4 gene promoter activity in cultured HEK-293 and INS-1 cells. Furthermore, the variant (32124C > T) evidently enhanced the binding of unknown transcriptional activator.CONCLUSIONS:
Our data suggested that GATA4 gene regulatory variants may contribute to T2D development as a rare risk factor.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Variation
/
Polymorphism, Single Nucleotide
/
Diabetes Mellitus, Type 2
/
GATA4 Transcription Factor
Type of study:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
BMC Endocr Disord
Year:
2021
Document type:
Article
Affiliation country:
China