Genetic Determinants of Type 2 Diabetes
The 1000 Genomes Project evidenced the need to study the genetic variability of various populations of the world. The human genome has common or rare variations greater than 1% in the DNA sequence, which gives us different specific phenotypical characteristics among individuals or populations. The term used to name these variations is genetic polymorphism, which refers to the existence within a population of multiple alleles of a gene. Thanks to the genome-wide association study (GWAS), in the last few years, more than 80 signals associated with the phenotype for type 2 diabetes (T2D) have been identified and validated in various populations of the world. Currently, the use of technological tools, together with the sequencing of exomes, has identified a small panel of genetic markers associated with the phenotype for T2D, which can have certain clinical use in the prevention, diagnosis, prognosis, and pharmacological therapy. In conclusion, the GWAS has offered important knowledge of the genetic variants most associated with T2D in the world, highlighting TCFL2, ABCC8, CAPN10, PPAR, CDNKN2A/B, CDKAL1, and IGF2BP2 genes. Other markers are only found to be important in some ethnic groups, so it is a priority to analyze them, in order to have answers for early diagnosis and treatment in specific populations. Pharmacogenomic and pharmacogenetic studies will generate more knowledge for personalized treatment in different populations.
KeywordsType 2 diabetes Gene Genetic determinants Single nucleotide polymorphism Ancestry
- 11.Villarreal-Molina MT, Flores-Dorantes MT, Arellano-Campos O, Villalobos-Comparan M, Rodriguez-Cruz M, Miliar-Garcia A, et al. Association of the ATP-binding cassette transporter A1 R230C variant with early-onset type 2 diabetes in a Mexican population. Diabetes. 2008;57(2):509–13.CrossRefGoogle Scholar
- 12.Cahua-Pablo JA, Cruz M, Tello-Almaguer PV, del Alarcón-Romero LC, Parra EJ, Villerías-Salinas S, Valladares-Salgado A, Tello-Flores VA, Méndez-Palacios A, Pérez-Macedonio CP, Flores-Alfaro E. Analysis of admixture proportions in seven geographical regions of the State of Guerrero, Mexico. Am J Hum Biol. 2017;29. (Submitted).Google Scholar
- 16.Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, et al. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes. 2003;52(2):568–72.CrossRefGoogle Scholar
- 29.Burguete-Garcia AI, Cruz M, Madrid-Marina V, Lopez-Ridaura R, Hernández-Avila M, Cortina B, et al. Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: a candidate gene study. Metabolism. 2010;59:38–45.CrossRefGoogle Scholar
- 35.Below JE, Gamazon ER, Morrison JV, Konkashbaev A, Pluzhnikov A, McKeigue PM, et al. Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals. Diabetologia. 2011;54(8):2047–55.CrossRefGoogle Scholar