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• W3154013580 abstract "Abstract Background Type 2 diabetes mellitus (T2D) is a common and complex disease. Dysfunction of pancreatic β 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." @default.
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• W3154013580 date "2021-04-17" @default.
• W3154013580 modified "2023-09-24" @default.
• W3154013580 title "Identification and functional study of GATA4 gene regulatory variants in type 2 diabetes mellitus" @default.
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• W3154013580 doi "https://doi.org/10.1186/s12902-021-00739-0" @default.
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