alexa A Polymorphic Microdeletion in the RGS9 Gene Suppresses
ISSN: 2155-6156

Journal of Diabetes & Metabolism
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Research Article

A Polymorphic Microdeletion in the RGS9 Gene Suppresses PTB Binding and Associates with Obesity

Chong Shen1, Meenakshi Sharma2, Daniel C Reid3, Pengtao Li4, Jeremy Celver2, Norhashimah Abu Seman5,6, Jinfeng Chen1, Senthil K Vasan5, Hairu Wang1, Tianwei Gu5, Ying Liu4, Wan Nazaimoon Wan Mohamud6, Hongbing Shen1, Kerstin Brismar5, William G Fairbrother3, Abraham Kovoor2* and Harvest F Gu5

1Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, PR China

2Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island, USA

3Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, USA

4National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine, Peking Union Medical College, Beijing, P. R. China

5Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

6Cardiovascular, Diabetes and Nutrition Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia

*Corresponding Author:
Abraham Kovoor
Department of Biomedical and Pharmaceutical Sciences
College of Pharmacy, University of Rhode Island
Kingston, Rhode Island, USA
Tel: +1 401 874 4727
E-mail: [email protected]

Received date: August 20, 2014; Accepted date: September 18, 2014; Published date: September 24, 2014

Citation: Shen C, Sharma M, Reid DC, Li P, Celver J, et al. (2014) A Polymorphic Microdeletion in the RGS9 Gene Suppresses PTB Binding and Associates with Obesity. J Diabetes Metab 5:437. doi: 10.4172/2155-6156.1000437

Copyright: © 2014 Shen C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Objective: RGS9 is a member of the family of Regulators of G-Protein Signaling (RGS) proteins defined by the presence of an RGS domain which can accelerate the GTPase-activity of G protein Gα subunits. An insertion/deletion (I/D) polymorphism of the nucleotide sequence TTTCT (rs3215227) has been identified in the human RGS9 gene, which matches the consensus high affinity binding motif for the ubiquitously expressed RNA binding Polypyrimidine Tract Binding Protein (PTB). In this study, we evaluate the genetic association and functional relevance of this polymorphism in type 2 diabetes and obesity.

Subjects and methods: We genotyped a larger population of 9272 Chinese and Malaysian individuals for the RGS9 I/D polymorphism using Taq Man allelic discrimination protocols. We found that the D allele of the RGS9 polymorphism was associated with a decreased prevalence of obesity in women (P=0.003, OR=0.753 95%CI 0.625-0.906) and girls (P=0.002, OR=0.604 95%CI 0.437-0.835). The association was moderate in boys (P=0.038, OR=0.724 95%CI 0.533-0.983) and not significant in men. Furthermore, we found that the transcript deletion variant exhibited a 10-fold reduction in PTB binding in vitro and that the splicing of the deletion variant was less affected by PTB co-expression.

Conclusions: We provide genetic and biochemical data to support a genetic role of RGS9 in obesity but unlikely in T2D. The RGS9 I/D polymorphism influence the post-transcriptional processing of the gene through an altered affinity for the splicing factor PTB and are associated with obesity.

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