The Impact of the PCK1 gene and PPCK1 promoter polymorphism 232CÆG on the incidence of TIIDM in Oji-Cree natives of Ontario Francisco J Grajales III Bioinformatics Research Laboratory, Trinity Western University, Langley, BC, V2Y 1Y1
Introduction Results Conclusions
In 1999 the WHO predicted a 39% rate increase on the 1. Due to the complexity of TIIDM, prevention and incidence of diabetes between 2000 and 2030. (1) Several management strategies for type 2 diabetes should apply studies have calculated that Canada surpassed this astonishing apply multi-tier treatment and prevention strategies. astonishing rate last year in 2006. Worldwide more than 150 2. Further research is needed to evaluate the different genes 150 million people suffer from type II diabetes and it is genes and their specific correlation with the incidence of calculated to cost an average of 5-15% of world health budgets of type II diabetes. budgets depending on the country. 3. Molecules fitting into the active site of cystolic phosphoenolpyruvate carboxykinease (PCK1) need to be The prevalence of TIIDM in Ontario Ojibwa-Cree Natives is be engineered in order to develop future treatments for type is approximately 2 in every 5. Highest from any subpopulation for type II diabetes. subpopulation in the world, the Oji-Cree desperately need 4. Alternate pathways, particularly with respect to need intervention strategies from a disease that “is killing transcription regulation need to be investigated to find [their] people”. Understanding the genetic component of this find alternative treatment strategies for type 2 diabetes. this disease may help identify the different metabolic pathways diabetes. pathways involved in diabetes and allow for faster intervention 5. The direct effect of Metformin on PEPCK translation is yet intervention strategies for the prevention and treatment of is yet to be understood. of diabetes. Fig. 2. The specific impact of TIIDM is a heterogeneous disease where cells become glucose PEPCK on glucose intolerant and insulin resistant. Studies have shown Gluconeogenesis. (4) shown that genetic predisposition plays a larger role than environment on the incidence of the disease. Most reported Literature cited reported cases of TIIDM are polygenic and are caused when an (1) Cao, H., Van Der Veer, E., Ban, M.R., Hanley, A.J.G., Zinman, B., Harris, S.B., Young, T.K., Pickering, when an individual’s environment (mainly diet and exercise) Pickering, J.G. AND Hegele, R.A. 2004. Promoter Polymorphism in PCK1 (Phosphoenolpyruvate exercise) and genetic background interact. Chromosomes 1, 2, (Phosphoenolpyruvate Caboxykinase Gene) Associated with Type 2 Diabetes Mellitus. The Journal Journal of Clinical Endocrinology & Metabolism 89, 898-903. 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 16, 19, 20, and X have been (2) Dunten, P., Belunis, C., Crowther, R., Hollfelder, K., Kammlott, U., Levin, W., Michel, H., Ramsey, Ramsey, G.B., Swain, A., Weber, D. and Wertheiner, S.J. 2002. Crystal Structure of Human linked to the occurrence of type II diabetes. PCK1, located in Cytosolic Physphoenolpyruvate Carboxykinase Reveals a New GTP-binding Site. J Molecular located in chromosome 20q13.2, is among these candidate Molecular Biology 316, 257-264. (3) Hegele, R.A., Zinman, B., Hanley, A.J.G., Harris, S.B., Barrett, P.H. and Cao, H. 2003. Genes, candidate genes. environment and Oji-Cree type 2 diabetes. Clinical Biochemistry 36, 163-170. (4) Inoue, E. and Yamauchi, J. 2006. AMP-activated protein kinase regulates PEPCK gene expression by expression by direct phosphorylation of a novel zinc finger transcription factor. Biochemical and and Biophysical Research Communications 351, 793-799. (5) KEGG: Kyoto Encyclopedia of Genes and Genomes 2007. Type II diabetes mellitus - Homo sapiens sapiens (human).