- 作者：Suwattanee Kooptiwut ; Nattachet Plengvidhya ; Titikan Chukijrungroat ; Jatuporn Sujjitjoon ; Namoiy Semprasert ; Hiroto Furuta ; Pa-thai Yenchitsomanus
- 关键词：Maturity onset diabetes of the young ; Early onset-age of type 2 diabetes ; PAX4 polymorphism ; PAX4 R192H ; Thais
- 刊名：Journal of Diabetes and its Complications
- 出版年：2012
- 出版时间：July-August, 2012
- 年：2012
- 卷：26
- 期：4
- 页码：343-347
- 全文大小：510 K
Aims
PAX4 R192H polymorphism was reported to be associated with maturity onset diabetes of the young (MODY) and early onset-age of type 2 diabetes (T2D). This study aimed to evaluate transcriptional repression activity of PAX4 R192H polymorphism on its target promoters comparing with wild-type PAX4.Methods
Wild-type PAX4 and PAX4 R192H proteins were expressed in vitro and the cell compartmentalization of each protein was examined after transfection of the plasmid constructs into ¦ÂTC3 cells followed by Western-blot analysis. The plasmid containing wild-type PAX4 or PAX4 R192H was co-transfected into ¦ÂTC3 and ¦ÁTC-1.9 cells with insulin or glucagon promoter-reporter construct. Transcriptional repression activities were then determined by dual-luciferase reporter assay.
Results
Wild-type PAX4 and PAX4 R192H, which were found to be equally expressed in vitro and transfection systems, were present in the nuclear compartment. Transcriptional repressor activities of PAX4 R192H on human insulin and glucagon promoters were reduced when they were compared with those of wild-type PAX4.
Conclusions
These results suggested that PAX4 R192H polymorphism generated a protein with defect in transcriptional repressor activities on its target genes, which may lead to ¦Â-cell dysfunction associated with MODY and early onset-age of T2D as reported in our previous study.