Genetic causes of diabetes mellitus type 2 - wikipedia Genetic causes of diabetes mellitus type 2 Most cases of diabetes mellitus type 2 involved many genes contributing small amount to the overall condition. As of 2011 more than 36 genes have been found that contribute to the risk of type 2 diabetes. All of these genes together still only account for 10 % of the total genetic component of the disease. There are a number of rare cases of diabetes that arise due to an abnormality in a single gene ( known as monogenic forms of diabetes ). These include maturity onset diabetes of the young ( MODY ), Donohue syndrome, and Rabson -- Mendenhall syndrome, among others. Maturity onset diabetes of the young constitute 1 -- 5 % of all cases of diabetes in young people. Polygenic Genetic cause and mechanism of type 2 diabetes is largely unknown. However, single nucleotide polymorphism ( SNP ) is one of many mechanisms that leads to increased risk for type 2 diabetes. To locate genes and loci that are responsible for the risk of type 2 diabetes, genome wide association studies ( GWAS ) was utilized to compare the genomes of diabetic patient group and the non-diabetic control group. The diabetic patients ' genome sequences differ from the controls ' genome in specific loci along and around numerous genes, and these differences in the nucleotide sequences alter phenotypic traits that exhibit increased susceptibility to the diabetes. GWAS has revealed 65 different loci ( where single nucleotide sequences differ from the patient and control group 's genomes ), and genes associated with type 2 diabetes, including TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, IGF2BP2, SLC30A8, JAZF1, HHEX, DGKB, CDKN2A, CDKN2B, KCNQ1, HNF1A, HNF1B MC4R, GIPR, HNF4A, MTNR1B, PARG6, ZBED3, SLC30A8, CDKAL1, GLIS3, GCKR, among others. KCNJ11 ( potassium inwardly rectifying channel, subfamily J, member 11 ), encodes the islet ATP - sensitive potassium channel Kir6. 2, and TCF7L2 ( transcription factor 7 -- like 2 ) regulates proglucagon gene expression and thus the production of glucagon - like peptide - 1. In addition, there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes. However, this is not a comprehensive list of genes that affects the proneness to the diabetes. Most SNPs that increase the risk of diabetes reside in noncoding regions of the genes, making the SNP 's mechanism for increasing susceptibility largely unknown. However, they are thought to influence the susceptibility by altering the regulation of those gene expressions. Only few genes ( PARG6, KCNJ11 - ABCC8, SLC30A8, and GCKR ) have SNPs in the open reading frame ( ORF ). These SNPs in ORFs result in altering of the protein function, and the altered function and therefore compromise the performances of the protein product causes increased susceptibility to the type 2 diabetes. One of the examples of gene regulation in non-ORF SNPs that influences susceptibility is the changes in nucleotide sequence in microRNA ( miRNA ) binding site. miRNAs regulate gene expression by binding to the target mRNAs and physically block translation. SNPs on the miRNA - binding site can result in faulty levels of gene expression as miRNA fails to bind to the corresponding mRNA effectively, leading to excess amount of protein product overall. Although the protein structure of the genes with SNPs are identical to that of the normal gene product, due to their faulty level of expressions, those genes increase risk. Genes such as CDKN2A, CDKN2B, and HNF1B exhibit increase the risk phenotype with SNPs in their 3 ' UTR miRNA binding sites. As CDKN2A and B regulate the pancreatic beta - cell replication, and HNF1B is homeodomain containing transcription factor that regulates other genes, faulty regulations of those genes increase the risk of diabetes. Another example of faulty gene regulation that influence the susceptibility is the SNPs in promoter regions of the genes. Gene like APOM and APM1 increase the risk of type 2 diabetes when there are SNPs in their proximal promoter regions. Promoters are sequences of DNA that allows proteins such as transcription factors to bind for gene expression, and when the sequences are modified, the proteins no longer bind as effectively, resulting in depressed level of gene expression. APOM is partly responsible for producing pre beta - high - density lipoprotein and cholesterol, and APM1 is responsible for regulating glucose level in blood and fatty acid. Decreasing the level these gene products reduce the body 's ability to handle glucose, which leads to the increased risk of diabetes. It is important to note that those discovered genes do not determine susceptibility to diabetes for all people or cases. As the risk of diabetes is combination of the gene regulations and the interplay between those gene products, certain genes may not pose a threat to increase the susceptibility. TCF7L2 is one of the well - studied genes for diabetes susceptibility in most populations. However, SNPs in TCF7L2 that would normally increase the risk of diabetes does not affect the susceptibility for Pima Indians. However, this gene is associated with regulating the BMI for Pima Indian population. Various hereditary conditions may feature diabetes, for example myotonic dystrophy and Friedreich 's ataxia. Wolfram 's syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD. While obesity is an independent risk factor for type 2 diabetes that may be linked to lifestyle, obesity is also a trait that may be strongly inherited. Other research also shows that type 2 diabetes can cause obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance. However, environmental factors ( almost certainly diet and weight ) play a large part in the development of type 2 diabetes in addition to any genetic component. Genetic risk for type 2 diabetes changes as humans first began migrating around the world, implying a strong environmental component has affected the genetic - basis of type 2 diabetes. This can be seen from the adoption of the type 2 diabetes epidemiological pattern in those who have moved to a different environment as compared to the same genetic pool who have not. Immigrants to Western developed countries, for instance, may be more prone to diabetes as compared to its lower incidence in their countries of origins. Such developments can also be found in environments which have had a recent increase in social wealth, increasingly common throughout Asia. See also Epigenetics of diabetes Type 2 References ^ Jump up to : Williams textbook of endocrinology ( 12th ed. ). Philadelphia : Elsevier / Saunders. pp. 1371 -- 1435. ISBN 978 - 1 - 4377 - 0324 - 5. ^ Jump up to : Herder, C ; Roden, M ( Jun 2011 ). `` Genetics of type 2 diabetes : pathophysiologic and clinical relevance ''. European Journal of Clinical Investigation. 41 ( 6 ) : 679 -- 92. doi : 10.1111 / j. 1365 - 2362.2010. 02454. x. PMID 21198561. Jump up ^ `` Monogenic Forms of Diabetes : Neonatal Diabetes Mellitus and Maturity - onset Diabetes of the Young ''. National Diabetes Information Clearinghouse ( NDIC ). National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Retrieved 2008 - 08 - 04. ^ Jump up to : Gaulton, Kyle ( Dec 2015 ). `` Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci ''. Nature Genetics. 47 : 1415 -- 25. doi : 10.1038 / ng. 3437. PMC 4666734. PMID 26551672. Jump up ^ Lyssenko V, Jonsson A, Almgren P, et al. ( November 2008 ). `` Clinical risk factors, DNA variants, and the development of type 2 diabetes ''. The New England Journal of Medicine. 359 ( 21 ) : 2220 -- 32. doi : 10.1056 / NEJMoa0801869. PMID 19020324. Jump up ^ McCarthy, M.I. ( December 2010 ). Feero, W.G. ; Guttmacher, A.E., eds. `` Genomics, Type 2 Diabetes, and Obesity ''. The New England Journal of Medicine. 363 ( 24 ) : 2339 -- 50. doi : 10.1056 / NEJMra0906948. PMID 21142536. Jump up ^ Ayub, Qasim ( Feb 6, 2014 ). `` Revisiting the Thrifty Gene Hypothesis via 65 Loci Associated with Susceptibility to Type 2 Diabetes ''. American Society of Human Genetics. 94 : 176 -- 85. doi : 10.1016 / j. ajhg. 2013.12. 010. PMC 3928649. PMID 24412096. Jump up ^ Rother KI ( April 2007 ). `` Diabetes treatment -- bridging the divide ''. The New England Journal of Medicine. 356 ( 15 ) : 1499 -- 501. doi : 10.1056 / NEJMp078030. PMC 4152979. PMID 17429082. Jump up ^ Sakagashira S, Sanke T, Hanabusa T, et al. ( September 1996 ). `` Missense mutation of amylin gene ( S20G ) in Japanese NIDDM patients ''. Diabetes. 45 ( 9 ) : 1279 -- 81. doi : 10.2337 / diabetes. 45.9. 1279. PMID 8772735. Jump up ^ Cho YM, Kim M, Park KS, Kim SY, Lee HK ( May 2003 ). `` S20G mutation of the amylin gene is associated with a lower body mass index in Korean type 2 diabetic patients ''. Diabetes Res. Clin. Pract. 60 ( 2 ) : 125 -- 9. doi : 10.1016 / S0168 - 8227 ( 03 ) 00019 - 6. PMID 12706321. Retrieved 19 July 2008. Jump up ^ Wang, Xiaojing ( Oct 2015 ). `` Association study of the miRNA - binding site polymorphisms of CDKN2A / B genes with gestational diabetes mellitus susceptibility ''. Acta Diabetologica. 52 : 951 -- 8. doi : 10.1007 / s00592 - 015 - 0768 - 2. PMID 25990668. Jump up ^ Goda, Naoki ( Sep 2, 2015 ). `` Polymorphism in microRNA - binding site in HNF1B influences the susceptibility of type 2 diabetes mellitus : a population based case - control study ''. BMC Medical Genetics. 16 : 75. doi : 10.1186 / s12881 - 015 - 0219 - 5. PMC 4557749. PMID 26329304. Jump up ^ Niu, Nifang ( Jan 2007 ). `` Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene ( apoM ) confer the susceptibility to development of type 2 diabetes in Han Chinese ''. Diabetes / Metabolism Research and Reviews. 23 : 21 -- 5. doi : 10.1002 / dmrr. 641. PMID 16572495. Jump up ^ Gu, HF ( Feb 2004 ). `` Single nucleotide polymorphisms in the proximal promoter region of the adiponectin ( APM1 ) gene are associated with type 2 diabetes in Swedish Caucasians ''. Diabetes. 53 Suppl 1 : S31 -- 5. doi : 10.2337 / diabetes. 53.2007. S31. PMID 14749263. Jump up ^ Guo, Tingwei ( Dec 2007 ). `` TCF7L2 is not a major susceptibility gene for type 2 diabetes in Pima Indians ''. Diabetes. 56 : 3082 -- 8. doi : 10.2337 / db07 - 0621. PMID 17909099. Jump up ^ Barrett TG ( September 2001 ). `` Mitochondrial diabetes, DIDMOAD and other inherited diabetes syndromes ''. Best Practice & Research. Clinical Endocrinology & Metabolism. 15 ( 3 ) : 325 -- 43. doi : 10.1053 / beem. 2001.0149. PMID 11554774. Jump up ^ Walley AJ, Blakemore AI, Froguel P ( October 2006 ). `` Genetics of obesity and the prediction of risk for health ''. Human Molecular Genetics. 15 Spec No 2 : R124 -- 30. doi : 10.1093 / hmg / ddl215. PMID 16987875. Jump up ^ `` Can Diabetes Type II be inherited ? ''. Dw.com. 25 August 2017. Retrieved 29 August 2017. Jump up ^ Camastra S, Bonora E, Del Prato S, Rett K, Weck M, Ferrannini E ( December 1999 ). `` Effect of obesity and insulin resistance on resting and glucose - induced thermogenesis in man. EGIR ( European Group for the Study of Insulin Resistance ) ''. Int. J. Obes. Relat. Metab. Disord. 23 ( 12 ) : 1307 -- 13. doi : 10.1038 / sj. ijo. 0801072. PMID 10643689. Jump up ^ Corona, Erik. `` Geneworld ''. World Wide Patterns of Genetic Risk for Disease. Stanford University. Retrieved 11 September 2013. Jump up ^ Gibbons, Ann ( 4 November 2011 ). `` Diabetes Genes Decline Out of Africa ''. Science. 334 ( 6056 ) : 583. doi : 10.1126 / science. 334.6056. 583. PMID 22053022. Jump up ^ Cotran, Kumar, Collins ; Robbins Pathologic Basis of DiseaseSaunders Sixth Edition, 1999 ; 913 - 926. Diabetes ( E10 -- E14, 250 ) Types Type 1 Type 2 LADA Gestational diabetes Diabetes and pregnancy Prediabetes Impaired fasting glucose Impaired glucose tolerance Insulin resistance KPD MODY Neonatal Transient Permanent Type 3c ( Pancreatogenic ) Blood tests Blood sugar level Glycosylated hemoglobin Glucose tolerance test Postprandial glucose test Fructosamine Glucose test C - peptide Noninvasive glucose monitor Insulin tolerance test Management Diabetic diet Anti-diabetic drugs Insulin therapy intensive conventional pulsatile Cure Embryonic stem cells Artificial pancreas Other Gastric bypass surgery Complications Diabetic comas Hypoglycemia Ketoacidosis Hyperosmolar hyperglycemic state Diabetic foot ulcer Neuropathic arthropathy Organs in diabetes Blood vessels Muscle Kidney Nerves Retina Heart Diabetic skin disease Diabetic dermopathy Diabetic bulla Diabetic cheiroarthropathy Neuropathic ulcer Hyperglycemia Hypoglycemia Other Glossary of diabetes Notable people with type 1 diabetes Retrieved from `` https://en.wikipedia.org/w/index.php?title=Genetic_causes_of_diabetes_mellitus_type_2&oldid=810376518 '' Categories : Diabetes Talk About Wikipedia Add links This page was last edited on 14 November 2017, at 21 : 49. 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Question: a population group that has a genetic susceptibility to type 2 diabetes is
Answer: Immigrants to Western developed countries