Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 31237
Analysis of Metallothionein Gene MT1A (rs11076161) and MT2A (rs10636) Polymorphisms as a Molecular Marker in Type 2 Diabetes Mellitus among Malay Population

Authors: Norsakinah Mohammad Osman, Ali Etemad, Patimah Ismail

Abstract:

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that characterized by the presence of high glucose in blood that cause from insulin resistance and insufficiency due to deterioration β-cell Langerhans functions. T2DM is commonly caused by the combination of inherited genetic variations as well as our own lifestyle. Metallothionein (MT) is a known cysteine-rich protein responsible in helping zinc homeostasis which is important in insulin signaling and secretion as well as protection our body from reactive oxygen species (ROS). MT scavenged ROS and free radicals in our body happen to be one of the reasons of T2DM and its complications. The objective of this study was to investigate the association of MT1A and MT2A polymorphisms between T2DM and control subjects among Malay populations. This study involved 150 T2DM and 120 Healthy individuals of Malay ethnic with mixed genders. The genomic DNA was extracted from buccal cells and amplified for MT1A and MT2A loci; the 347bp and 238bp banding patterns were respectively produced by mean of the Polymerase Chain Reaction (PCR). The PCR products were digested with Mlucl and Tsp451 restriction enzymes respectively and producing fragments lengths of (158/189/347bp) and (103/135/238bp) respectively. The ANOVA test was conducted and it shown that there was a significant difference between diabetic and control subjects for age, BMI, WHR, SBP, FPG, HBA1C, LDL, TG, TC and family history with (P<0.05). While the HDL, CVD risk ratio and DBP does not show any significant difference with (P>0.05). The genotype frequency for AA, AG and GG of MT1A polymorphisms was 72.7%, 22.7% and 4.7% in cases and 15%, 55% and 30% in control respectively. As for MT2A, genotype frequency of GG, GC and CC was 42.7%, 27.3% and 30% in case and 5%, 40% and 55% for control respectively. Both polymorphisms show significant difference between two investigated groups with (P=0.000). The Post hoc test was conducted and shows a significant difference between the genotypes within each polymorphism (P=0. 000). The MT1A and MT2A polymorphisms were believed to be the reliable molecular markers to distinguish the T2DM subjects from healthy individuals in Malay populations.

Keywords: Malay, Type 2 Diabetes Mellitus (T2DM), Metallothionein (MT), MT1A (rs11076161), MT2A (rs10636), Genetic Polymorphism

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1086729

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 2013

References:


[1] Arora, N., & Chertow, G. M. (2011). Update in nephrology: evidence published in 2010. Annals of internal medicine, 154(12), 824-829.
[2] Cai, L. (2004). Metallothionein as an adaptive protein prevents diabetes and its toxicity. Nonlinearity in Biology, Toxicology, and Medicine, 2(2), 89-103.
[3] Chen, H., Carlson, E. C., Pellet, L., Moritz, J. T., & Epstein, P. N. (2001). Overexpression of metallothionein in pancreatic β-cells reduces streptozotocin-induced DNA damage and diabetes. Diabetes, 50(9), 2040-2046.
[4] Chen, X., Lei, L., Tian, L., Zhu, G., & Jin, T. (2012). Bone mineral density and polymorphisms in metallothionein 1A and 2A in a Chinese population exposed to cadmium. Science of the Total Environment, 423, 12-17.
[5] Cipriano, C., Malavolta, M., Costarelli, L., Giacconi, R., Muti, E., Gasparini, N., ... & Mocchegiani, E. (2006). Polymorphisms in MT1a gene coding region are associated with longevity in Italian Central female population. Biogerontology,7(5-6), 357-365.
[6] Ganasyam, S. R., Rao, T. B., Murthy, Y. S. R., Jyothy, A., & Sujatha, M. (2012). Association of Estrogen Receptor-α Gene & Metallothionein- 1 Gene Polymorphisms in Type 2 Diabetic Women of Andhra Pradesh. Indian Journal of Clinical Biochemistry, 27(1), 69-73.
[7] Letchuman, G. R., Wan Nazaimoon, W. M., Wan Mohamad, W. B., Chandran, L. R., Tee, G. H., Jamaiyah, H., ... & Ahmad Faudzi, Y. (2010). Prevalence of diabetes in the Malaysian national health morbidity survey III 2006. Med J Malaysia, 65(3), 180-186.
[8] Riaz, S., Alam, S. S., Srai, S. K., Skinner, V., Riaz, A., & Akhtar, M. W. (2010). Proteomic identification of human urinary biomarkers in diabetes mellitus type 2. Diabetes technology & therapeutics, 12(12), 979-988.
[9] Saltiel, A. R. (2001). New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell, 104(4), 517.
[10] Skutkova, H., Babula, P., Stiborova, M., Eckschlager, T., Trnkova, L., Provaznik, I., ... & Adam, V. (2012). Structure, Polymorphisms and Electrochemistry of Mammalian Metallothioneins–A Review. Int. J. Electrochem. Sci, 7, 12415-12431.
[11] Van-Tilburg, J., Van Haeften, T. W., Pearson, P., & Wijmenga, C. (2001). Defining the genetic contribution of type 2 diabetes mellitus. Journal of medical genetics, 38(9), 569-578.
[12] Wild, S. H., Roglic, G., Green, A., Sicree, R., & King, H. (2004). Global Prevalence of Diabetes: Estimates for the Year 2000 and Projections for 2030 Response to Rathman and Giani. Diabetes care, 27(10), 2569- 2569.
[13] Yang, L., Li, H., Yu, T., Zhao, H., Cherian, M. G., Cai, L., & Liu, Y. (2008). Polymorphisms in metallothionein-1 and-2 genes associated with the risk of type 2 diabetes mellitus and its complications. American Journal of Physiology-Endocrinology And Metabolism, 294(5), E987- E992.