GENETIC MARKERS OF TYPE 2 DIABETES

Authors

  • V. A. Musiienko І. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY
  • M. I. Marushchak І. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY

DOI:

https://doi.org/10.11603/mcch.2410-681X.2019.v.i4.10688

Keywords:

genetic markers, type 2 diabetes, gene polymorphism

Abstract

Introduction. Type 2 diabetes (T2D) is a global health problem due to rapid cultural and social change, aging of the population, increasing urbanization, changing nutrition, and reduced physical activity. Some risk factors can be controlled, such as diet and obesity, while others, such as sex, age, genetics, are beyond our control. Diabetes mellitus type 2 is believed to be a polygenic disorder that develops through a complex interaction between several genes and environmental factors. The first evidence of the role of genetic markers in the development of type 2 diabetes was twin studies in large families conducted in the second half of the XX century. The first candidate genes were identified for rare forms of diabetes (neonatal, mitochondrial CD, MODY). There are currently many genetic markers for T2D known, but the pathogenetic link between most of them remains to be confirmed. However, this is only a small fraction of the genetic component of the disease. The pace of research into the complex genetics of T2D has been impressive over the last decade. Currently, there are over 300 loci that are closely related to T2D. The most studied and those of considerable scientific interest are the KCNJ11, TCF7L2, PPARG, IRS1, PON 1, SLC30A8, FTO and TNF-alpha genes. It is worth noting that the role of genes in the pathogenesis of diabetes is ambiguous and needs further investigation.

The aim of the study – to analyze current literary sources about genetic markers that are involved in the mechanisms of type 2 diabetes.

Conclusions. Analysis of literature sources substantiates the relevance of the study of genetic factors in the pathogenesis of type 2 diabetes. Defining the role of gene polymorphism in the development and progression of type 2 diabetes will open the way for new approaches to the diagnosis, stratification, monitoring, prevention and treatment of this disease.

References

Zheng, Y., Ley, S. & Hu, F. (2018). Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol., 14, 88-98.

Kaiser, A.B., Zhang, N., & Van Der Pluijm, W. (2018). Global prevalence of type 2 diabetes over the next ten years (2018-2028). Diabetes, 67 (1), 202.

Saddik, B., & Al-Dulaijan, N. (2015). Diabetic patients’ willingness to use tele-technology to manage their disease - A descriptive study. Online J. Public Health Inform, 7 (2), e214. doi:10.5210/ojphi.v7i2.6011

Sun, W. Yao, S., Tang, J., Liu, S., Chen, J., & Deng, D. (2018). Integrative analysis of superenhancer SNPs for type 2 diabetes. PLoS ONE, 13 (1).

Forouhi, N.G., & Wareham, N. J. (2019). Epidemiology of diabetes. Medicine, 47 (1), 22-27.

Ali, O. (2013). Genetics of type 2 diabetes. World J. Diabetes, 4 (4), 114-123.

Scott, R.A., Scott, L.J., Mägi, R., Marullo, L., Gaulton, K.J. Kaakinen, M., … et al. (2017). Diabetes genetics replication and meta-analysis (DIAGRAM) consortium. An expanded genome-wide association study of type 2 diabetes in Europeans. Diabetes, 66 (11), 2888-2902. doi:10.2337/db16-1253

Mahajan, A., Taliun, D., Thurner, M., Robert­son, N.R., Torres, J.M., Rayner, N. W., . . . McCarthy, M.I. (2018). Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat. Genet., 50 (11), 1505-1513. doi:10.1038/s41588-018-0241-6

Khan, V., Bhatt, D., Khan, S., VERMA, A.K., Hasan, R., Rafat, S., ... Dev, K. (2019). Association of KCNJ11 genetic variations with risk of type 2 diabetes mellitus (T2DM) in North Indian population. Preprints, 2019070089 doi: 10.20944/preprints201907.0089.v1

Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., ... Froguel, P. (2007). A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature, 445 (7130), 881-885. doi:10.1038/nature05616

Koster, J.C., Marshall, B.A., Ensor, N., Corbett, J.A., & Nichols, C.G. (2000). Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. Cell, 100 (6), 645-654. doi:10.1016/s0092-8674(00)80701-1

Fakruddin, M. (2019). Genetics of type 2 diabetes: A review. Journal of Current and Advance Medical Research, 6 (1), 59-63.

Ding, W., Xu, L., Zhang, L., Han, Z., Jiang, Q., Wang, Z. & Jin, S. (2018). Meta-analysis of association between TCF7L2 polymorphism rs7903146 and type 2 diabetes mellitus. BMC Medical Genetics, 19 (1).

Cauchi, S., Meyre, D., Choquet, H., Dina, C., Born, C., Marre, M., ... Group, D.S. (2006). TCF7L2 variation predicts hyperglycemia incidence in a French general population: the data from an epidemiological study on the Insulin Resistance Syndrome (DESIR) study. Diabetes, 55 (11), 3189-3192. doi:10.2337/db06-0692

Migliorini, A., & Lickert, H. (2015). Beyond association: A functional role for Tcf7l2 in beta-cell development. Mol. Metab., 4 (5), 365-366. doi:10.1016/j.molmet.2015.03.002

Dalhat, M., Bello, H., Ibrahim, B. & Labbo, A. (2017). Association of rs7903146 TCF7L2 (C/T) Gene polymorphism and type 2 diabetes mellitus in Pakistani population. Journal of Applied Life Sciences International, 14 (4), 1-7.

Huang, Z., Liao, Y., Huang, R., Chen, J. & Sun, H. (2018). Possible role of TCF7L2 in the pathogenesis of type 2 diabetes mellitus. Biotechnology & Biotechnological Equipment, 32 (4), 830-834.

Ip, W., Chiang, Y.T., & Jin, T. (2012). The involvement of the wnt signaling pathway and TCF7L2 in diabetes mellitus: The current understanding, dispute, and perspective. Cell Biosci., 2 (1), 28. doi:10.1186/2045-3701-2-28

Kersten, S., Desvergne, B., & Wahli, W. (2000). Roles of PPARs in health and disease. Nature, 405 (6785), 421-424. doi:10.1038/35013000

Zeggini, E., Weedon, M.N., Lindgren, C.M., Frayling, T.M., Elliott, K.S., Lango, H., ... Hattersley, A.T. (2007). Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science, 316 (5829), 1336-1341. doi:10.1126/science.1142364

Muoio, D.M., & Newgard, C.B. (2008). Mecha­nisms of disease: Molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat. Rev. Mol. Cell Biol., 9(3), 193-205. doi:10.1038/nrm2327

Jakobsen, S.N., Hardie, D.G., Morrice, N., & Tornqvist, H.E. (2001). 5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxa­mide riboside. J. Biol. Chem., 276 (50), 46912-46916. doi:10.1074/jbc.C100483200

Ijaz, A., Babar, S., Sarwar, S., Shahid, S.U., & Shabana. (2019). The combined role of allelic variants of IRS-1 and IRS-2 genes in susceptibility to type2 diabetes in the Punjabi Pakistani subjects. Diabetol. Metab. Syndr., 11, 64. doi:10.1186/s13098-019-0459-1

Mahmutovic, L., Bego, T., Sterner, M., Grems­perger, G., Ahlqvist, E., Velija Asimi, Z., ... Semiz, S. (2019). Association of IRS1 genetic variants with glucose control and insulin resistance in type 2 diabetic patients from Bosnia and Herzegovina. Drug Metab. Pers. Ther., 34 (1). doi:10.1515/dmpt-2018-0031

Shalimova, A. (2015). Asotsiatsii polimorfizmu hena irs-1 z porushenniamy lipidnoho spektra krovi pry hipertonichnii khvorobi i suputnоmu tsukrovomu diabeti 2-ho typu [Association of IRS>1 gene polymorphism with violations of blood lipid spectrum in patients with essential hypertension and concomitant type 2 diabetes]. Semeynaya medytsyna – Family Medicine, 3, 102-104 [in Ukrainian].

Zhang, D., Zhang, X., Liu, D., Liu, T., Cai, W., Yan, C., & Han, Y. (2016). Association between insulin receptor substrate-1 polymorphisms and high platelet reactivity with clopidogrel therapy in coronary artery disease patients with type 2 diabetes mellitus. Cardiovasc. Diabetol., 15, 50. doi:10.1186/s12933-016-0362-0

Lavin, D.P., White, M.F., & Brazil, D.P. (2016). IRS proteins and diabetic complications. Diabetologia, 59 (11), 2280-2291. doi:10.1007/s00125-016-4072-7

Gong, L., Li, R., Ren, W., Wang, Z., Wang, Z., Yang, M., & Zhang, S. (2017). The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population. J. Korean Med. Sci., 32 (2), 264-271. doi:10.3346/jkms.2017.32.2.264

Precourt, L.P., Amre, D., Denis, M.C., Lavoie, J.C., Delvin, E., Seidman, E., & Levy, E. (2011). The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis, 214 (1), 20-36. doi:10.1016/j.atherosclerosis.2010.08.076

Mackness, M., & Mackness, B. (2015). Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles. Gene, 567 (1), 12-21. doi:10.1016/j.gene.2015.04.088

Levy, D., Reichert, C.O., & Bydlowski, S.P. (2019). Paraoxonases activities and polymorphisms in elderly and old-age diseases: An overview. Antioxidants (Basel), 8 (5). doi:10.3390/antiox8050118

Shunmoogam, N., Naidoo, P., & Chilton, R. (2018). Paraoxonase (PON)-1: a brief overview on ge­netics, structure, polymorphisms and clinical relevance. Vasc. Health Risk Manag., 14, 137-143. doi:10.2147/VHRM.S165173

Costa, L.G., Cole, T.B., Vitalone, A., & Furlong, C.E. (2005). Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity. Clin. Chim. Acta, 352 (1-2), 37-47. doi:10.1016/j.cccn.2004.09.019

Bacchetti, T., Ferretti, G., & Sahebkar, A. (2019). The role of paraoxonase in cancer. Semin. Cancer Biol., 56, 72-86. doi:10.1016/j.semcancer.2017.11.013

Tamaki, M., Fujitani, Y., Hara, A., Uchida, T., Tamura, Y., Takeno, K., ... Watada, H. (2013). The diabe­tes-susceptible gene SLC30A8/ZnT8 regulates hepatic insulin clearance. J. Clin. Invest., 123 (10), 4513-4524. doi:10.1172/JCI68807

Gu, H.F. (2017). Genetic, epigenetic and biolo­gical effects of zinc transporter (SLC30A8) in type 1 and type 2 diabetes. Curr. Diabetes Rev., 13 (2), 132-140. doi:10.2174/1573399812666151123104540

Billings, L.K., Jablonski, K.A., Ackerman, R.J., Taylor, A., Fanelli, R.R., McAteer, J.B., . . . Diabetes Prevention Program Research Group, R. (2014). The influence of rare genetic variation in SLC30A8 on diabetes incidence and beta-cell function. J. Clin. Endocrinol. Metab., 99 (5), E926-930. doi:10.1210/jc.2013-2378

Khan, I.A., Jahan, P., Hasan, Q., & Rao, P. (2015). Validation of the association of TCF7L2 and SLC30A8 gene polymorphisms with post-transplant diabetes mellitus in Asian Indian population. Intractable Rare Dis. Res., 4 (2), 87-92. doi:10.5582/irdr.2015.01008

Salem, S.D., Saif-Ali, R., Ismail, I.S., Al-Hamodi, Z., & Muniandy, S. (2014). Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study. BMC Endocr. Disord., 14, 2. doi:10.1186/1472-6823-14-2

Cheng, L., Zhang, D., Zhou, L., Zhao, J., & Chen, B. (2015). Association between SLC30A8 rs13266634 polymorphism and type 2 diabetes risk: A meta-analysis. Med. Sci. Monit., 21, 2178-2189. doi:10.12659/MSM.894052

Lin, Y., Li, P., Cai, L., Zhang, B., Tang, X., Zhang, X., ... Yang, Z. (2010). Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population. BMC Med. Genet., 11, 97. doi:10.1186/1471-2350-11-97

Kanoni, S., Nettleton, J. A., Hivert, M.F., Ye, Z., van Rooij, F.J., Shungin, D., ... Dedoussis, G.V. (2011). Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis. Diabetes, 60 (9), 2407-2416. doi:10.2337/db11-0176

Nikitin, A.G., Potapov, V.Y., Brovkina, O.I., Kok­sharova, E.O., Khodyrev, D.S., Philippov, Y.I., ... Shestakova, M.V. (2017). Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population. PeerJ., 5, e3414. doi:10.7717/peerj.3414

Sabarneh, A., Ereqat, S., Cauchi, S., AbuSham­ma, O., Abdelhafez, M., Ibrahim, M., & Nasereddin, A. (2018). Common FTO rs9939609 variant and risk of type 2 diabetes in Palestine. BMC Med. Genet., 19 (1), 156. doi:10.1186/s12881-018-0668-8

Kamura, Y., Iwata, M., Maeda, S., Shinmura, S., Koshimizu, Y., Honoki, H., ... Tobe, K. (2016). FTO gene polymorphism is associated with type 2 diabetes through its effect on increasing the maximum BMI in Japanese men. PLoS One, 11 (11), e0165523. doi:10.1371/journal.pone.0165523

Ghafarian-Alipour, F., Ziaee, S., Ashoori, M.R., Zakeri, M.S., Boroumand, M.A., Aghamohammadzadeh, N., ... Zarghami, N. (2018). Association between FTO gene polymorphisms and type 2 diabetes mellitus, serum levels of apelin and androgen hormones among Iranian obese women. Gene, 641, 361-366. doi:10.1016/j.gene.2017.10.082

Moller, D.E. (2000). Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol. Metab., 11 (6), 212-217. doi:10.1016/s1043-2760(00)00272-1

Lorenzo, M., Fernandez-Veledo, S., Vila-Bed­mar, R., Garcia-Guerra, L., De Alvaro, C., & Nieto-Vaz­quez, I. (2008). Insulin resistance induced by tumor necrosis factor-alpha in myocytes and brown adipocytes. J. Anim. Sci., 86 (14), E94-104. doi:10.2527/jas.2007-0462

Kubaszek, A., Pihlajamaki, J., Punnonen, K., Karhapaa, P., Vauhkonen, I., & Laakso, M. (2003). The C-174G promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity. Diabetes, 52 (2), 558-561. doi:10.2337/diabetes.52.2.558

Yamashina, M., Kaneko, Y., Maesawa, C., Kajiwara, T., Ishii, M., Fujiwara, F., ... Satoh, J. (2007). Association of TNF-alpha gene promoter C-857T poly­morphism with higher serum LDL cholesterol levels and carotid plaque formation in Japanese patients with type 2 diabetes. Tohoku J. Exp. Med., 211 (3), 251-258. doi:10.1620/tjem.211.251

Nadeem, A. (2017). Inter-ethnic variations in association of TNF-alpha G308a single nucleotide polymorphism with type 2 diabetes mellitus – a review. Journal of Diabetes, Metabolic Disorders & Control, 4 (2). doi: 10.15406/jdmdc.2017.04.00105

Published

2020-01-30

How to Cite

Musiienko, V. A., & Marushchak, M. I. (2020). GENETIC MARKERS OF TYPE 2 DIABETES. Medical and Clinical Chemistry, (4), 184–191. https://doi.org/10.11603/mcch.2410-681X.2019.v.i4.10688

Issue

Section

REVIEWS