list of genes involved in type 2 diabetes

What are the differences between type 1 and type 2 diabetes? Biomed. Shoily, S.S., Ahsan, T., Fatema, K. et al. J. Clin. The majority of genetic variations associated with type 2 diabetes are thought to act by subtly changing the amount, timing, and location of gene activity (expression). The authors declare no competing interests. Approved drugs, that target these candidate genes, are listed in Table 3. Type 2 diabetes mellitus and cardiovascular disease: Genetic and epigenetic links. contracts here, Sign up for Nature Briefing: Translational Research. Huang, T., Shu, Y. Therefore, population specific genetic architectures should be considered before considering a drug for these conditions. Nucleic Acids Res. Again, efficacy of losartan might be more in treating diabetes associated complications in the European populations. Lyssenko V, Tuomi T, Isomaa B, Hunter DJ, Qi L; Wellcome Trust Case Control https://doi.org/10.1007/s40265-019-1064-1 (2019). Chem. J. Endocrinol. 2015, 508409. https://doi.org/10.1155/2015/508409 (2015). Type 2 diabetes mellitus (T2DM) is a metabolic disorder. Eyries, M. et al. Veglia F, Wennauer R, Winckler W, Zabaneh D, Campbell H, van Duijn C, At these loci the MAFs are> 0.2 in two admixed American sub-populations (Puerto Ricans from Puerto Rico and Colombians from Medellin, Colombia). You can also try going for a walk during lunch. Thirty six target genes involved in type 2 diabetes and four genes associated with anorexia nervosa were investigated for gene expression in small intestinal biopsies from 144 children with celiac disease at median (range) age of 7.4 years (1.617.8) and from 154 disease controls at a median (range) age 11.4.years (1.418.3). Google Scholar. Clinical and metabolic characteristics of the Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I) randomised clinical trial cohort. HIF-1 contributes to the hypoxia induced regulation of apelin and the apelin receptor88 to stimulate cell proliferation and angiogenesis via PI3K-Akt and mTOR mediated processes89. Genetic associations between genes in the renin-angiotensin-aldosterone system and renal disease: A systematic review and meta-analysis. 2016, 6809703. https://doi.org/10.1155/2016/6809703 (2016). Only haplotypes with frequency of0.05 in at least one super-population were listed. RA, Segre AV, Sehmi J, Sennblad B, Shah N, Shah S, Shera AS, Shu XO, Shuldiner TLR4 activation can contribute to insulin resistance by proinflammatory cytokines in diabetes91. Anders, H. J. In addition, IL6 may impair insulin mediated IRS-1/PI3-kinase/Akt pathway by activating c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase-1/2 (ERK1/2), which in turn induce serine phosphorylation of IRS-177. Tay WT, Teslovich TM, Thorand B, Thorleifsson G, Thorsteinsdottir U, Tikkanen E, Federal government websites often end in .gov or .mil. Pancreatic RAAS plays an important role in the pathophysiology of diabetes38. https://doi.org/10.1038/nrc1187 (2003). Single nucleotide polymorphisms (SNPs) involved in insulin resistance, weight regulation, lipid metabolism and inflammation in relation to metabolic syndrome: An epidemiological study. The ADA notes that it is possible to help prevent type 2 diabetes by exercising and reaching or maintaining a moderate weight. Nat Genet. WY, Stancakova A, Stefansson K, Steinbach G, Steinthorsdottir V, Stirrups K, Eur. The ADA also advises that race can also play a role, and research indicates a higher prevalence among Asian, Black, and Latino people. The findings provide evidence of a direct link between genetic factors associated with susceptibility to type 1 diabetes and immune functionality, particularly involving immune T cells. In people with diabetes, anti-hypertensive medications reduce microvascular complications as well as ASCVD events7. These studies were complicated by the environmental influences that also affect type 2 diabetes risk. https://doi.org/10.4239/wjd.v5.i6.809 (2014). In addition to calculating the probability whether a mutation is damaging by estimating the false positive rate (FPR, the chance that the mutation is classified as damaging when it is in fact non-damaging) and the true positive rate (TPR, the chance that the mutation is classified as damaging when it is indeed damaging), PolyPhen-2 also classifies a mutation qualitatively as-benign,possibly damaging, orprobably damagingbased on false positive rate (FPR) thresholds. How can gene variants affect health and development? As the community embraces complementary approaches that include systematic fine-mapping, custom-made replication, denser genotyping arrays, platforms that focus on functional variation, next-generation sequencing techniques, systems biology approaches, and expansion to non-European populations, the coming years will witness exponential growth in the understanding of the genetic architecture of metabolic phenotypes. 9, 2. https://doi.org/10.3389/fendo.2018.00002 (2018). Liu CT, Liu JJ, Lobbens S, Long J, Loos RJ, Lu W, Luan J, Lyssenko V, Ma RC, From January 2014 to October 2017, 1564 unrelated patients with a personal and/or a family history of hyperglycemia or diabetes and consecutively referred for genetic screening by 116 departments of Endocrinology and Diabetology throughout France were included in this study (Additional file 1: List of Investigators). 2010 Nov;1212:59-77. doi: 10.1111/j.1749-6632.2010.05838.x. WebGenetics of type 2 diabetes mellitus. Monday, July 11, 2016 Genetics of type 2 diabetes revealed in unprecedented detail What A comprehensive investigation of the underlying genetic architecture of type 2 diabetes has unveiled the most detailed look at the genetic differences that heighten a persons risk for disease development. Learn more about. Bonnycastle LL, Burtt N, Carey J, Charpentier G, Crenshaw AT, Doney AS, Dorkhan 4, 115. Higher levels of this cytokine have been found in diabetic patients compared to non-diabetic controls44. Krishnasamy, S. et al. Genetic variants associated with chronic kidney disease in a Spanish population. Environmental factors, such as obesity in the case of type 2 diabetes, also play a part in the development of polygenic forms of diabetes. Additionally, angiotensin II stimulates the expression of transforming growth factor- (TGF-) in the kidney, which play significant roles in the development of diabetic nephropathy71. Interestingly, rs1045642, a variant in the multi-drug transporter ABCB1 (also known as MDR1 and P-gp), is in strong linkage disequilibrium with rs1800795 (IL6) and rs1799983 (NOS3) (Supplementary Table S2). 11, 576632. https://doi.org/10.3389/fendo.2020.576632 (2020). 47, D607D613. However, for many of the variations that have been associated with type 2 diabetes, the mechanism by which they contribute to disease risk is unknown. ISSN 2045-2322 (online). IL-6 induction of TLR-4 gene expression via STAT3 has an effect on insulin resistance in human skeletal muscle. Hamoudi, R. et al. Bethesda, MD 20894, Web Policies Hyperglycemia accelerates the formation of advanced glycation end products (AGEs), which interact with their major cell surface signal transduction receptor for AGE (RAGE) on smooth muscle cells, endothelial cells and monocytes, thereby inducing a wide range of signaling pathways65,67. Within these subdivisions, people remixed and settled in widely varying environments, which resulted in the shuffling of genes leading to genetic heterogeneity. Role of interleukin-6 in depressive disorder. See additional information. Hypertens. https://doi.org/10.1161/JAHA.118.009890 (2018). Carriers of the variant allele (C) at rs5186 may have better humoral and renal hemodynamic responses to losartan treatment compared to individuals with the AA genotype106. Eye 24, 15761584. : Design of the study; S.S.S., T.A. https://doi.org/10.1590/s0004-27302008000800027 (2008). Disparities in the variant allele frequencies among different ethnic regions may contribute to varied disease susceptibilities28. Nat. Google Scholar. Swaroop, J. J., Rajarajeswari, D. & Naidu, J. N. Association of TNF- with insulin resistance in type 2 diabetes mellitus. Willemsen G, et al. Besides these HLA haplotypes and the insulin region that importantly contribute to the heritable component, genome-wide association studies have identified many polymorphisms in over 60 non-HLA gene regions that also contribute to T1D susceptibility. A persons genes can make them more susceptible to developing type 2 diabetes, and the disease has a stronger link to family history than type 1 diabetes. care.diabetesjournals.org/content/41/Supplement_1/S13, cdc.gov/diabetes/basics/risk-factors.html, diabetes.org/diabetes-basics/genetics-of-diabetes.html, diabetes.diabetesjournals.org/content/58/6/1350, niddk.nih.gov/health-information/diabetes/overview/risk-factors-type-2-diabetes, ncbi.nlm.nih.gov/pmc/articles/PMC5241767/, thelancet.com/journals/landia/article/PIIS2213-8587(20)30117-0/fulltext, https://onlinelibrary.wiley.com/doi/10.1111/ijcp.12384, cambridge.org/core/journals/twin-research-and-human-genetics/article/concordance-and-heritability-of-type-2-diabetes-in-34166-twin-pairs-from-international-twin-registers-the-discordant-twin-discotwin-consortium/94E0005D626FB0399AA8FDDAC82F970E. Database 2014, bau101, https://doi.org/10.1093/database/bau101 (2014). Aims: To identify the key differentially expressed genes (DEGs) in islet and investigate their potential pathway in the molecular process of type 2 Sci. BMC Nephrol. This proinflammatory cytokine along with elevated IL6 inhibits insulin signaling pathways and contributes to the development of diabetes82. 3rd edition. Hunt, S. E. et al. Lakka TA, Lind L, Dedoussis G, Njolstad I, Pedersen NL, Khaw KT, Wareham NJ, ROS also triggers nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), which is a key player in cytokine and inflammatory mediator expression that results in micro-vasculopathy65. This might result in low circulating level of vasodilator NO by the variant allele itself or its linkage with the causal variant(s). Machiela, M. J. -, Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H: Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerancea population-based twin study. The variant (T) allele at this position is associated with significantly reduced basal NO production60. The recognition of a monogenic form of diabetes dates back to the 1970s, when Robert Tattersall first described maturity-onset diabetes of the young (MODY). Trends Endocrinol. Ethnic differences in allele frequencies at drug response-related SNP loci contribute to inter-population variability in drug response103. 10, 9. https://doi.org/10.1186/1471-2369-10-9 (2009). Metab. https://doi.org/10.1046/j.1523-1755.1999.00770.x (1999). & Sun, R. Association between interleukin-6 rs 1800795 polymorphism and the decreased risk of type 2 diabetes mellitus: An updated meta-analysis. Heterogeneity in the distribution of 159 drug-response related SNPs in world populations and their genetic relatedness. The reason could be that the African Americans inherited approximately 80% of their genome from African ancestor and 20% from the Europeans103. Wong TY, Wood AR, Wu JY, Wu Y, Yamamoto K, Yamauchi T, Yang M, Yengo L, Yokota M, Muller-Nurasyid M, Pechlivanis S, Rayner NW, Scott LJ, Wiltshire S, Yengo L, PubMed Central 9;363(24):2339-50. doi: 10.1056/NEJMra0906948. Florez JC, Scott LJ, Morris AP, Kang HM, Boehnke M, Altshuler D, McCarthy MI. & Chanock, S. J. LDlink: A web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Other SNPs within the candidate genes, that harbor the common variants, in the above mentioned 26 populations were retrieved using the Ensembl allele frequency calculator116. HIF-1 binds DNA at the hypoxia response element (HRE) and activates expression of several hypoxia induced genes involved in glucose metabolism, angiogenesis, cell proliferation, survival and metastasis83. Article & Sessa, W. C. Nitric oxide synthases: Regulation and function. PubMed Central Thorand B, Hansen T, Meisinger C, Hu FB, Isomaa B, Karpe F, Liang L, Peters A, Ligand-engagement of RAGE triggers activation of NADPH oxidase, which leads to generation of reactive oxygen species (ROS), that in turn can activate renin-angiotensin system (RAS)68. Diabetes is a multifactorial endocrine disorder which heightens the chances of developing other complex conditions33. Strawbridge RJ, Stringham HM, Sun Q, Suo C, Syvanen AC, Takayanagi R, Takeuchi F, Salomaa V, Saltevo J, Samuel M, Sanghera DK, Saramies J, Scott J, Scott LJ, Scott Piccoli, J. C. E. et al. Deloukas P, Dimas AS, Dina C, Doney AS, Donnelly PJ, Dorkhan M, van Duijn C, ZBTB16, also known as promyelocytic leukemia zinc finger (PLZF), is a transcription factor (TF) that is be related to cardiac hypertrophy and/or fibrosis associated with hypertension and connected to components of metabolic syndrome such as dyslipidemia and insulin resistance via TNFA and IL697. Circ. Int. Abstract. SNPcurator is text mining system that extracts information from the genome wide and candidate genes studies113. Poulsen P, et al. 21, 2194. https://doi.org/10.3390/ijms21062194 (2020). Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 14. 6, 17. https://doi.org/10.1186/1758-5996-6-17 (2014). 1). It arises as a consequence of autoimmune destruction of pancreatic -cells, resulting in insufficient insulin production. Curr. Companies such as 23andMe offer this type of test. Test. 9, 2941. https://doi.org/10.1038/s41467-018-04951-w (2018). Geographically, diabetes is most prevalent in the southern and Appalachian regions of the United States. Endocrinol. Such interplay among diabetes and associated complications hint towards common contributing factors. From choosing baby's name to helping a teenager choose a Only four SNPs (rs5186, rs1800629, rs1799983, and rs1800795) were found to have association with diabetes, cardiovascular diseases, diabetic nephropathy, diabetic retinopathy, hypertension, inflammation, and kidney diseases. https://doi.org/10.1093/nar/gkw1092 (2017). Discussion. Last medically reviewed on August 24, 2021. Eur. https://doi.org/10.1128/MCB.01340-06 (2007). But because genes can change expression due to environmental factors, people can influence whether they develop type 2 diabetes with diet and lifestyle strategies. Google Scholar. T2D Knowledge Portal Researchers have built a public database, the T2D Knowledge Portal, of DNA sequence, functional genomic and epigenomic information, and clinical data from studies on type 2 diabetes and its cardiac and renal complications. Type 2 Diabetes which happens to be thenon-insulin dependent one is the most common form of the disease and is caused by the interaction between genetic and non-genetic factors. Despite conflicting results, numerous studies have identified genetic and non-genetic factors associated with this common type of diabetes. https://doi.org/10.2337/diacare.28.9.2280 (2005). Frequencies of the variant allele (C) at rs5186 are high in the European and the admixed American populations (Table 1). A 2020 review outlines lifestyle factors that studies have associated with the disease and may lead to obesity, oxidative stress, and insulin resistance. et al. PMC -. J. Renin-Angiotensin-Aldosterone Syst. Epub 2017 Feb 10. DGIdb 3.0: A redesign and expansion of the druggene interaction database. In the South Asian population, A allele of rs5186 acts as a protective factor against renal disease development34. A.A.S. Rep. 6, 32677. https://doi.org/10.1038/srep32677 (2016). World J. Diabetes 6, 850867. The overall MAFs at rs5186, rs1799983 and rs1800795 in the European super-population are 0.272, 0.344 and 0.416, respectively. doi: 10.1042/BSR20182172. Biomark. M, Barroso I, Wilsgaard T, Beilby J, Hovingh K, Price JF, Wilson JF, Rauramaa R, Andersen, C. U., Hilberg, O., Mellemkjr, S., Nielsen-Kudsk, J. E. & Simonsen, U. Apelin and pulmonary hypertension. This missense variant resides in the exon 7 of NOS3 gene. New research finds that gastric bypass surgery can help people achieve long-term diabetes remission regardless of how much weight is lost. This study aimed to identify potential core genes and pathways involved in T2DM, through exhaustive bioinformatic analyses using GSE20966 microarray profiles of pancreatic cells Curr Vasc Pharmacol. Type 2 diabetes has a stronger link to family history and lineage than type 1, and studies of twins have shown that genetics play a very strong role in the development As mentioned earlier, the C allele at the rs5186 locus affects translation of AGTR1 leading to increased activation of the reninangiotensinaldosterone system. In addition, environmental factors such as diet, exercise, and infection can result in epigenetic changes. Combination of genetic variants and physiologically characterized pathways improves the classification of individuals with T2D into subgroups, and is also paving the Diabetes Obes. But it does increase your chance of getting it. Peer Review reports Background https://doi.org/10.1089/gtmb.2017.0220 (2018). Border, W. A. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: Systematic review and meta-analyses. The importance of weight management in type 2 diabetes mellitus. Physiol. Lancet. Am. Metab. In this form of diabetes, the body stops using and making insulin properly. Montecucco, F., Pende, A. Rahmani M, Earp MA, Ramezani Tehrani F, Ataee M, Wu J, Treml M, Nudischer R, P-Behnami S; ReproGen Consortium; Perry JR, Murabito JM, Azizi F, Brooks-Wilson A. Hum Reprod. Abstract A large proportion of heritability of type 2 diabetes (T2D) has been attributed to inherent genetics. Physiol. This inductive role of IL-1 is outlined in the supplementary Fig. The risk of developing type 2 diabetes increases with the number of affected family members. Joseph, J. J. et al. Indian J. Med. Insulin is a hormone produced in the pancreas that helps regulate blood sugar levels. https://doi.org/10.1530/JOE-14-0397 (2015). Wishart, D. S. et al. Additionally, increased amount of urea in blood in individuals with chronic kidney disease causes defect in insulin secretion from the pancreatic cells13. Rep. 39, 12931303. High prevalence of overweight and obesity in the European populations49 may exacerbate the effect of this variant allele, which is highly prevalent at this locus. You can learn more about how we ensure our content is accurate and current by reading our. Biomed. How are genetic conditions treated or managed? The https:// ensures that you are connecting to the The Ensembl variant effect predictor. (2013). DNA test company 23andMe rolls out type 2 diabetes risk report (2019). J, Lam VKL, Park KS, Saleheen D, So WY, Tam CHT, Afzal U, Aguilar D, Arya R, Aung According to the National Diabetes Statistics Report 2020, more than 34 million Americans have diabetes (about 1 in 10), and approximately 9095% of them have type 2 diabetes. 2014 Mar;46(3):234-44. doi: Kay, A. M., Simpson, C. L. & Stewart, J. & Morishima, K. KEGG: New perspectives on genomes, pathways, diseases and drugs. It is, therefore, not impossible to have an underlying link among these conditions. Google Scholar. 2016 Sep;17(9):535-49. doi: Navarro, J. F., Milena, F. J., Mora, C., Len, C. & Garca, J. Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: Effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. We explored their possible interplay in diabetes and associated complications. Debbie C. Thurmond, Ph.D.City of Hope's presence at this year's ADA conference Nat. Spanakis, E. K. & Golden, S. H. Race/ethnic difference in diabetes and diabetic complications.
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