AIM: The development of Type 2 diabetes mellitus (T2DM) has been recognized to be associated with a combination of pancreatic beta-cell dysfunction and insulin resistance. Nuclear factor-kappaB (NF-kappaB) has been recognized as one central mediator in the reaction of inflammation and proapoptotic event in beta-cells. A functional polymorphism at the codon 55 (methionine to valine; A163G) of the small ubiquitin- like modifier-4 (SUMO4) gene may result in higher NF-kappaB activity. This study investigates whether this SUMO4 Met55Val polymorphism also contributes to the development of T2DM. MATERIALS AND METHODS: The study was performed using genomic DNA samples from 574 Type 2 diabetic patients and 323 healthy controls. The SUMO4 Met55Val polymorphism was genotyped using allele-specific real-time PCR. RESULTS: The frequency of the G allele (encoding Val55) was significantly higher in Type 2 diabetic patients and Type 2 diabetic patients with the GG genotype had higher hemoglobin A1c level. Multivariate logistic regression analysis revealed the genotype of GG and GA was an independent risk factor contributing to the development of T2DM. CONCLUSION: This study suggests that in Taiwan the SUMO4 Met 55Val polymorphism is associated with susceptibility to T2DM and Type 2 diabetic patients with GG genotype have worse glycemic control.
AIM: The development of Type 2 diabetes mellitus (T2DM) has been recognized to be associated with a combination of pancreatic beta-cell dysfunction and insulin resistance. Nuclear factor-kappaB (NF-kappaB) has been recognized as one central mediator in the reaction of inflammation and proapoptotic event in beta-cells. A functional polymorphism at the codon 55 (methionine to valine; A163G) of the small ubiquitin- like modifier-4 (SUMO4) gene may result in higher NF-kappaB activity. This study investigates whether this SUMO4 Met55Val polymorphism also contributes to the development of T2DM. MATERIALS AND METHODS: The study was performed using genomic DNA samples from 574 Type 2 diabeticpatients and 323 healthy controls. The SUMO4 Met55Val polymorphism was genotyped using allele-specific real-time PCR. RESULTS: The frequency of the G allele (encoding Val55) was significantly higher in Type 2 diabeticpatients and Type 2 diabeticpatients with the GG genotype had higher hemoglobin A1c level. Multivariate logistic regression analysis revealed the genotype of GG and GA was an independent risk factor contributing to the development of T2DM. CONCLUSION: This study suggests that in Taiwan the SUMO4 Met 55Val polymorphism is associated with susceptibility to T2DM and Type 2 diabeticpatients with GG genotype have worse glycemic control.
Authors: D Ross Laybutt; Hideaki Kaneto; Wendy Hasenkamp; Shane Grey; Jean-Christophe Jonas; Dennis C Sgroi; Adam Groff; Christiane Ferran; Susan Bonner-Weir; Arun Sharma; Gordon C Weir Journal: Diabetes Date: 2002-02 Impact factor: 9.461