The Impact of the PCK1 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 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 resistant. Studies have shown . (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. 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 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 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). . (6) Lipscombe, L.L. and Hux J. E. 2007. Trends in diabetes prevalence, incidence, and mortality in Ontario, Fig. 3. 3D structure of Ontario, Canada 1995–2005: a population-based study. The Lancet: 369, 750-756 human PEPCK. (2) Methods Fig. 3. Make sure legends have enough detail to fully explain to the viewer what the results are. Note that for posters it is good to put A literature review was conducted on the incidence of type 2 Figuresome 1. Location“Materials of theand PCK methods” enzyme information in the diabetes within thepathway. figure (5)legends type 2 diabetes in the Ojibwa-Cree native population of or onto the figures themselves—it allows the M&m section to be Acknowledgments shorter, and gives viewer a sense of the experiment(s) even if they Ontario, Canada. Particular attention was placed to the PCK1 have skipped directly to figures. Don’t be tempted to reduce font size PCK1 gene and its location. During this time the significance The author of this work would like to express his extensive gratitude to Dr. in figure legends, axes labels, etc.—your viewers are probably most to Dr. Alma Barranco-Mendoza and Dr. Deryck Persaud for their help, significance of SNP 231 CÆG was also being evaluated. The interested in reading your figures and legends! help, guidance, and continuous support throughout this project. The author The PCK1 sequence was then acquired from NCBI and author would also like to thank Amir and Daniel for granting me some of translated in six different ways by the EXPASY translation some of their parent time for the accomplishment of this project. translation tool. The resulting sequences (those between stop stop and start codons) of 65 amino acids in length or greater greater were then evaluated. Subsequently amino acid and Fig. 4. Localization of PCK1 to and nucleotide homology searches were conducted on each of Table 1. PCK1 232CÆG Single Nucleotide Polymorphism allele and genotype chromosome 20q13 by For further information each of these sequences. An emphasis was placed on the frequencies in Oji-Cree and Caucasian populations. (1) FISH. (1) If you would like a copy or have nay questions with regards to this research different biochemical pathways of PCK1 involvement. research please contact Francisco Grajales at [email protected]