The genetic side of type 2 diabetes - A review.

AIM Type 2 diabetes (T2DM) is a complex disease. Interactions between genetic susceptible variants and environmental cues results in the development of this heterogenous disease. Having an understanding of the genetics of T2DM may lead to a better perspective and management of the pathogenesis contributing to T2DM. MATERIALS AND METHODS Published primary and secondary sources were reviewed covering the keywords "genetics + type 2 diabetes" using PubMed and Google Scholar as the main databases. Full articles were considered when the title and the abstract was found to be sufficiently related to the review's aim. RESULTS Various genetic aspects of T2DM were summarised including a general understanding of the heritability and heterogeneity of T2DM. Furthermore, an explanation of the different genetic modalities that can be used to identify T2DM susceptible genes was provided. CONCLUSION In this day and era, researchers and healthcare professionals working in the field of metabolic disorders should have an understanding of T2DM genetics. The future lies in preventive and management action plans targeting the combination of genetics and environmental risk factors for a better health outcome.

[1]  Xavier Estivill,et al.  Disorders: Filling the Gaps and Exploring Complexity in Genome-Wide Association Studies , 2022 .

[2]  M. McCarthy,et al.  Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes , 2007, Science.

[3]  Xenophon Papademetris,et al.  High Visceral and Low Abdominal Subcutaneous Fat Stores in the Obese Adolescent , 2008, Diabetes.

[4]  T. Manolio,et al.  How to Interpret a Genome-wide Association Study Topic Collections , 2022 .

[5]  H. Cordell Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans. , 2002, Human molecular genetics.

[6]  C. Savona-Ventura,et al.  Starvation and the development of the metabolic syndrome , 2007 .

[7]  L. Groop,et al.  Antibodies to Glutamic Acid Decarboxylase Reveal Latent Autoimmune Diabetes Mellitus in Adults With a Non—Insulin-Dependent Onset of Disease , 1993, Diabetes.

[8]  M. Mancini,et al.  Separate influence of dietary carbohydrate and fibre on the metabolic control in diabetes , 1984, Diabetologia.

[9]  R. Myers,et al.  Candidate-gene approaches for studying complex genetic traits: practical considerations , 2002, Nature Reviews Genetics.

[10]  M. McCarthy,et al.  The genetics of type 2 diabetes. , 2001, Best practice & research. Clinical endocrinology & metabolism.

[11]  Francis S. Collins,et al.  Variations on a Theme: Cataloging Human DNA Sequence Variation , 1997, Science.

[12]  David J Hunter,et al.  From Darwin's finches to canaries in the coal mine--mining the genome for new biology. , 2008, The New England journal of medicine.

[13]  M. Laakso,et al.  Genetics of Type 2 Diabetes. , 2016, Endocrine development.

[14]  H. Stefánsson,et al.  Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes , 2006, Nature Genetics.

[15]  P. McKeigue,et al.  Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years , 1996, BMJ.

[16]  E. Lander,et al.  On the allelic spectrum of human disease. , 2001, Trends in genetics : TIG.

[17]  S. Dufour,et al.  Interethnic Differences in Muscle, Liver and Abdominal Fat Partitioning in Obese Adolescents , 2007, PloS one.

[18]  R. Bain,et al.  Predictors of Progression From Impaired Glucose Tolerance to NIDDM: An Analysis of Six Prospective Studies , 1997, Diabetes.

[19]  J. Köbberling,et al.  Age-Corrected Empirical Genetic Risk Estimates for First-Degree Relatives of IDDM Patients , 1987, Diabetes.

[20]  Michael Stumvoll,et al.  Type 2 diabetes: principles of pathogenesis and therapy , 2005, The Lancet.

[21]  C. Osmond,et al.  Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth , 2004, Diabetologia.

[22]  M. J. Charron,et al.  Minireview: Epigenetic programming of diabetes and obesity: animal models. , 2012, Endocrinology.

[23]  P. Poulsen,et al.  Heritability of Type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance – a population-based twin study , 1999, Diabetologia.

[24]  J. Vijg,et al.  SNP discovery in associating genetic variation with human disease phenotypes. , 2005, Mutation research.

[25]  Alison M. Goate,et al.  The Candidate Gene Approach , 2000, Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism.

[26]  C. Wijmenga,et al.  Defining the genetic contribution of type 2 diabetes mellitus , 2001, Journal of medical genetics.

[27]  R. Tattersall Mild familial diabetes with dominant inheritance. , 1974, The Quarterly journal of medicine.

[28]  A. Fritsche,et al.  Pathomechanisms of type 2 diabetes genes. , 2009, Endocrine reviews.

[29]  M. Daly,et al.  Genome-wide association studies for common diseases and complex traits , 2005, Nature Reviews Genetics.

[30]  S. Kahn,et al.  Mechanisms linking obesity to insulin resistance and type 2 diabetes , 2006, Nature.

[31]  T. Hudson,et al.  A genome-wide association study identifies novel risk loci for type 2 diabetes , 2007, Nature.

[32]  K. Abdullah,et al.  The TaqMan method for SNP genotyping. , 2009, Methods in molecular biology.

[33]  L. Cannon-Albright,et al.  Familiality of diabetes mellitus. , 2007, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[34]  M. Patti,et al.  The emerging genetic architecture of type 2 diabetes. , 2008, Cell metabolism.

[35]  H. Cordell Detecting gene–gene interactions that underlie human diseases , 2009, Nature Reviews Genetics.

[36]  M. King,et al.  Concordance for Type 2 (non-insulin-dependent) diabetes mellitus in male twins , 1987, Diabetologia.

[37]  C Osmond,et al.  Fetal and infant growth and impaired glucose tolerance at age 64. , 1991, BMJ.

[38]  N. Gungor,et al.  Progressive beta cell failure in type 2 diabetes mellitus of youth. , 2004, The Journal of pediatrics.

[39]  R. Bonadonna Alterations of Glucose Metabolism in Type 2 Diabetes Mellitus. An Overview , 2004, Reviews in Endocrine and Metabolic Disorders.

[40]  R. Tattersall,et al.  Maturity‐onset diabetes of the young: a clinical history , 1998, Diabetic medicine : a journal of the British Diabetic Association.

[41]  B. Maher Personal genomes: The case of the missing heritability , 2008, Nature.

[42]  K. Alberti,et al.  The classification and diagnosis of diabetes mellitus. , 2010, The New Zealand medical journal.

[43]  J. Pedersen The Pregnant Diabetic and Her Newborn. Problems and Management , 1968 .

[44]  P. Wilson,et al.  Parental transmission of type 2 diabetes: the Framingham Offspring Study. , 2000, Diabetes.

[45]  L. Cardon,et al.  Clustering of hypertension, diabetes, and obesity in adult male twins: same genes or same environments? , 1994, American journal of human genetics.

[46]  Lu Wang,et al.  SNP and mutation analysis. , 2007, Advances in experimental medicine and biology.

[47]  A. Hattersley,et al.  The fetal insulin hypothesis: an alternative explanation of the association of low bir thweight with diabetes and vascular disease , 1999, The Lancet.

[48]  P. Bennett,et al.  The natural history of impaired glucose tolerance in the Pima Indians. , 1988, The New England journal of medicine.

[49]  Y. Klimentidis,et al.  Identification of Allelic Heterogeneity at Type-2 Diabetes Loci and Impact on Prediction , 2014, PloS one.

[50]  Tiinamaija Tuomi,et al.  The many faces of diabetes: a disease with increasing heterogeneity , 2014, The Lancet.

[51]  Sonia Caprio,et al.  Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning , 2003, The Lancet.

[52]  Michael K Skinner,et al.  Environmental epigenetic transgenerational inheritance and somatic epigenetic mitotic stability , 2011, Epigenetics.

[53]  Mark I McCarthy,et al.  Learning From Molecular Genetics , 2008, Diabetes.

[54]  X. Papademetris,et al.  The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome , 2007, Proceedings of the National Academy of Sciences.

[55]  T. Mazza,et al.  Insights From Molecular Characterization of Adult Patients of Families With Multigenerational Diabetes , 2017, Diabetes.

[56]  D. Pyke,et al.  Diabetes in identical twins , 1981, Diabetologia.

[57]  Elias Zintzaras,et al.  Genome-wide association studies: hypothesis-"free" or "engaged"? , 2009, Translational research : the journal of laboratory and clinical medicine.

[58]  A. de Boer,et al.  Methodological and statistical issues in pharmacogenomics , 2010, The Journal of pharmacy and pharmacology.