ArticleBMC endocrine disorders2021
Identification and functional study of GATA4 gene regulatory variants in type 2 diabetes mellitus.
Article in BMC endocrine disorders, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 7 citations in OpenAlex.
- Cellular Senescence: A Bridge Between Diabetes and Microangiopathy.Biomolecules · 2024Review
- Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas.Nature communications · 2024Article
- Hepatic GATA4 regulates cholesterol and triglyceride homeostasis in collaboration with LXRs.Genes & developmentArticle
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7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundType 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.
methodsThe 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.
resultsThirteen 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.
conclusionsOur data suggested that GATA4 gene regulatory variants may contribute to T2D development as a rare risk factor.
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