Share This Article:

Association of TCF7L2 Gene Polymorphisms with T2DM in the Population of Juana Koslay, San Luis Province, Argentina

Full-Text HTML XML Download Download as PDF (Size:294KB) PP. 1-10
DOI: 10.4236/oalib.1101419    482 Downloads   666 Views  

ABSTRACT

Polymorphisms in the gene coding for transcription factor 7 like 2 (TCF7L2) are recognized as the strongest common genetic risk factors for Type 2 Diabetes Mellitus (T2DM) across multiple ethnicities. This study was conducted to evaluate an association between TCF7L2 variants and diabetes susceptibility in the population of Juana Koslay, San Luis, Argentina. We genotyped 2 single nucleotide polymorphisms (SNP) rs7903146 and rs12255372 in controls and diabetic subjects. Association with T2DM was found for both SNPs rs7903146 and rs12255372 in the whole sample (under a dominant genetic model, the odds ratios (OR) were 3.43, 95% CI [1.879 - 6.255], p < 0.0001 and OR = 4.40, 95% CI [2.318 - 8.351], p < 0.0001, respectively). The risk conferred by homozygotes is much higher than the heterozygote carriers and it is marked in case of rs7903146. The haplotype that consisted of two minor alleles (TT) or the haplotypes carrying at least one of the minor alleles at SNP rs7903146 or rs12255372 (i.e. CT or TG) were more frequent in the group of T2DM. The impact of TCF7L2 variation on T2DM risk in Juana Koslay population is compatible with that demonstrated by a range of studies conducted in various ethnic groups.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Siewert, S. , Márquez, F. , Mendoza, G. , Fernández, G. , González, I. and Ojeda, M. (2015) Association of TCF7L2 Gene Polymorphisms with T2DM in the Population of Juana Koslay, San Luis Province, Argentina. Open Access Library Journal, 2, 1-10. doi: 10.4236/oalib.1101419.

References

[1] American Diabetes Association (2003) Screening for Type 2 Diabetes. Diabetes Care, 26, S21-S24.
http://dx.doi.org/10.2337/diacare.26.2007.S21
[2] Shaw, J.E., Sicree, R.A. and Zimmet, P.Z. (2010) Global Estimates of the Prevalence of Diabetes for 2010 and 2030. Diabetes Research and Clinical Practice, 87, 4-14.
http://dx.doi.org/10.1016/j.diabres.2009.10.007
[3] Poulsen, P., Kyvik, K.O., Vaag, A. and Beck-Nielsen, H. (1999) Heritability of Type II (Non-Insulin-Dependent) Diabetes Mellitus and Abnormal Glucose Tolerance—A Population-Based Twin Study. Diabetologia, 42, 139-145.
http://dx.doi.org/10.1007/s001250051131
[4] Florez, J.C., Hirschhorn, J. and Altshuler, D. (2003) The Inherited Basis of Diabetes Mellitus: Implications for the Genetic Analysis of Complex Traits. Annual Review of Genomics and Human Genetics, 4, 257-291.
http://dx.doi.org/10.1146/annurev.genom.4.070802.110436
[5] Permutt, M.A., Wasson, J. and Cox, N. (2005) Genetic Epidemiology of Diabetes. The Journal of Clinical Investigation, 115, 1431-1439.
http://dx.doi.org/10.1172/JCI24758
[6] Grant, S.F., Thorleifsson, G., Reynisdottir, I., Benediktsson, R., Manolescu, A., Sainz, J., Helgason, A., Stefansson, H., Emilsson, V., Helgadottir, A., et al. (2006) Variant of Transcription Factor 7-Like 2 (TCF7L2) Gene Confers Risk of Type 2 Diabetes. Nature Genetics, 38, 320-323.
http://dx.doi.org/10.1038/ng1732
[7] Scott, L.J., Mohlke, K.L., Bonnycastle, L.L., Willer, C.J., Li, Y., Duren, W.L., Erdos, M.R., Stringham, H.M., Chines, P.S., Jackson, A.U., et al. (2007) A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants. Science, 316, 1341-1345.
http://dx.doi.org/10.1126/science.1142382
[8] Saxena, R., Voight, B.F., Lyssenko, V., Burtt, N.P., de Bakker, P.I., Chen, H., Roix, J.J., Kathiresan, S., Hirschhorn, J.N., Daly, M.J., et al. (2007) Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels. Science, 316, 1331-1336.
http://dx.doi.org/10.1126/science.1142358
[9] Zeggini, E., Weedon, M.N., Lindgren, C.M., Frayling, T.M., Elliott, K.S., Lango, H., Timpson, N.J., Perry, J.R., Rayner, N.W., Freathy, R.M., et al. (2007) Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes. Science, 316, 1336-1341.
http://dx.doi.org/10.1126/science.1142364
[10] Zhang, C., Qi, L., Hunter, D.J., Meigs, J.B., Manson, J.E., van Dam, R.M. and Hu, F.B. (2006) Variant of Transcription Factor 7-Like 2 (TCF7L2) Gene and the Risk of Type 2 Diabetes in Large Cohorts of U.S. Women and Men. Diabetes, 55, 2645-2648.
http://dx.doi.org/10.2337/db06-0643
[11] van Vliet-Ostaptchouk, J.V., Shiri-Sverdlov, R., Zhernakova, A., Strengman, E., van Haeften, T.W., Hofker, M.H. and Wijmenga, C. (2007) Association of Variants of Transcription Factor 7-Like 2 (TCF7L2) with Susceptibility to Type 2 Diabetes in the Dutch Breda Cohort. Diabetologia, 50, 59-62.
http://dx.doi.org/10.1007/s00125-006-0477-z
[12] Scott, L.J., Bonnycastle, L.L., Willer, C.J., Sprau, A.G., Jackson, A.U., Narisu, N., Duren, W.L., Chines, P.S., Stringham, H.M., Erdos, M.R., et al. (2006) Association of Transcription Factor 7-Like 2 (TCF7L2) Variants with Type 2 Diabetes in a Finnish Sample. Diabetes, 55, 2649-2653.
http://dx.doi.org/10.2337/db06-0341
[13] Saxena, R., Gianniny, L., Burtt, N.P., Lyssenko, V., Giuducci, C., Sjogren, M., Florez, J.C., Almgren, P., Isomaa, B., Orho-Melander, M., et al. (2006) Common Single Nucleotide Polymorphisms in TCF7L2 Are Reproducibly Associated with Type 2 Diabetes and Reduce the Insulin Response to Glucose in Nondiabetic Individuals. Diabetes, 55, 2890-2895.
http://dx.doi.org/10.2337/db06-0381
[14] Mayans, S., Lackovic, K., Lindgren, P., Ruikka, K., Agren, A., Eliasson, M. and Holmberg, D. (2007) TCF7L2 Polymorphisms Are Associated with Type 2 Diabetes in Northern Sweden. European Journal of Human Genetics, 15, 342-346.
http://dx.doi.org/10.1038/sj.ejhg.5201773
[15] Marzi, C., Huth, C., Kolz, M., Grallert, H., Meisinger, C., Wichmann, H.E., Rathmann, W., Herder, C. and Illig, T. (2007) Variants of the Transcription Factor 7-Like 2 Gene (TCF7L2) Are Strongly Associated with Type 2 Diabetes but Not with the Metabolic Syndrome in the MONICA/KORA Surveys. Hormone and Metabolic Research, 39, 46-52.
http://dx.doi.org/10.1055/s-2007-957345
[16] Humphries, S.E., Gable, D., Cooper, J.A., Ireland, H., Stephens, J.W., Hurel, S.J., Li, K.W., Palmen, J., Miller, M.A. and Cappuccio, F.P. (2006) Common Variants in the TCF7L2 Gene and Predisposition to Type 2 Diabetes in UK European Whites, Indian Asians and Afro-Caribbean Men and Women. Journal of Molecular Medicine, 84, 1-10.
http://dx.doi.org/10.1007/s00109-006-0108-7
[17] Helgason, A., Palsson, S., Thorleifsson, G., Grant, S.F., Emilsson, V., Gunnarsdottir, S., Adeyemo, A., Chen, Y., Chen, G., Reynisdottir, I., Benediktsson, R., et al. (2007) Refining the Impact of TCF7L2 Gene Variants on Type 2 Diabetes and Adaptive Evolution. Nature Genetics, 39, 218-225.
http://dx.doi.org/10.1038/ng1960
[18] Groves, C.J., Zeggini, E., Minton, J., Frayling, T.M., Weedon, M.N., Rayner, N.W., Hitman, G.A., Walker, M., Wiltshire, S., Hattersley, A.T., et al. (2006) Association Analysis of 6736 UK Subjects Provides Replication and Confirms TCF7L2 as a Type 2 Diabetes Susceptibility Gene with a Substantial Effect on Individual Risk. Diabetes, 55, 2640-2644.
http://dx.doi.org/10.2337/db06-0355
[19] Damcott, C.M., Pollin, T.I., Reinhart, L.J., Ott, S.H., Shen, H., Silver, K.D., Mitchell, B.D. and Shuldiner, A.R. (2006) Polymorphisms in the Transcription Factor 7-Like 2 (TCF7L2) Gene Are Associated with Type 2 Diabetes in the Amish: Replication and Evidence for a Role in both Insulin Secretion and Insulin Resistance. Diabetes, 55, 2654-2659.
http://dx.doi.org/10.2337/db06-0338
[20] Chandak, G.R., Janipalli, C.S., Bhaskar, S., Kulkarni, S.R., Mohankrishna, P., Hattersley, A.T., Frayling, T.M. and Yajnik, C.S. (2007) Common Variants in the TCF7L2 Gene Are Strongly Associated with Type 2 Diabetes Mellitus in the Indian Population. Diabetologia, 50, 63-67.
http://dx.doi.org/10.1007/s00125-006-0502-2
[21] Zhang, W., Duan, S., Bleibel, W.K., Wisel, S.A., Huang, R.S., Wu, X., He, L., Clark, T.A., Chen, T.X., Schweitzer, A.C., et al. (2008) Identification of Common Genetic Variants That Account for Transcript Isoform Variation between Human Populations. Human Genetics, 125, 81-93.
http://dx.doi.org/10.1007/s00439-008-0601-x
[22] Graham, R.R., Kozyrev, S.V., Baechler, E.C., Reddy, M.V., Plenge, R.M., Bauer, J.W., Ortmann, W.A., Koeuth, T., González Escribano, M.F., Pons-Estel, B., et al. (2006) A Common Haplotype of Interferon Regulatory Factor 5 (IRF5) Regulates Splicing and Expression and Is Associated with Increased Risk of Systemic Lupus Erythematosus. Nature Genetics, 38, 550-555.
http://dx.doi.org/10.1038/ng1782
[23] Lyssenko, V., Lupi, R., Marchetti, P., Del Guerra, S., Orho-Melander, M., Almgren, P., Sjögren, M., Ling, C., Eriksson, K.F., Lethagen, A.L., et al. (2007) Mechanisms by Which Common Variants in the TCF7L2 Gene Increase Risk of Type 2 Diabetes. Journal of Clinical Investigation, 117, 2155-2163.
http://dx.doi.org/10.1172/JCI30706
[24] Ahlzén, M., Johansson, L.E., Cervin, C., Tornqvist, H., Groop, L. and Ridderstråle, M. (2008) Expression of the Transcription Factor 7-Like 2 Gene (TCF7L2) in Human Adipocytes Is Down Regulated by Insulin. Biochemical and Biophysical Research Communications, 370, 49-52.
http://dx.doi.org/10.1016/j.bbrc.2008.03.006
[25] The Expert Committee of the Diagnosis and Classification of Diabetes Mellitus (1997) Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 20, 1183-1197.
http://dx.doi.org/10.2337/diacare.20.7.1183
[26] Friedewald, W.T., Levy, R.I. and Fredrickson, D.S. (1972) Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, without Use of the Preparative Ultracentrifuge. Clinical Chemistry, 18, 499-502.
[27] Ye, S., Dhillon, S., Ke, X., Collins, A.R. and Day, I.N. (2001) An Efficient Procedure for Genotyping Single Nucleotide Polymorphisms. Nucleic Acids Research, 29, E88.
http://dx.doi.org/10.1093/nar/29.17.e88
[28] Jin, T. (2008) The WNT Signalling Pathway and Diabetes Mellitus. Diabetologia, 51, 1771-1780.
http://dx.doi.org/10.1007/s00125-008-1084-y
[29] Yi, F., Brubaker, P.L. and Jin, T. (2005) TCF-4 Mediates Cell Type-Specific Regulation of Proglucagon Gene Expression by Beta-Catenin and Glycogen Synthase Kinase-3beta. The Journal of Biological Chemistry, 280, 1457-1464.
http://dx.doi.org/10.1074/jbc.M411487200
[30] Smith, U. (2007) TCF7L2 and Type 2 Diabetes—We WNT to Know. Diabetologia, 50, 5-7.
http://dx.doi.org/10.1007/s00125-006-0521-z
[31] Guo, T., Hanson, R.L., Traurig, M., Muller, Y.L., Ma, L., Mack, J., Kobes, S., Knowler, W.C., Bogardus, C. and Baier, L.J. (2007) TCF7L2 Is Not a Major Susceptibility Gene for Type 2 Diabetes in Pima Indians: Analysis of 3,501 Individuals. Diabetes, 56, 3082-3088.
http://dx.doi.org/10.2337/db07-0621
[32] Bodhini, D., Radha, V., Dhar, M., Narayani, N. and Mohan, V. (2007) The rs12255372(G/T) and rs7903146(C/T) Polymorphisms of the TCF7L2 Gene Are Associated with Type 2 Diabetes Mellitus in Asian Indians. Metabolism, 56, 1174-1178.
http://dx.doi.org/10.1016/j.metabol.2007.04.012
[33] Cauchi, S., El Achhab, Y., Choquet, H., Dina, C., Krempler, F., Weitgasser, R., Nejjari, C., Patsch, W., Chikri, M., Meyre, D., et al. (2007) TCF7L2 Is Reproducibly Associated with Type 2 Diabetes in Various Ethnic Groups: A Global Meta-Analysis. Journal of Molecular Medicine, 85, 777-782.
http://dx.doi.org/10.1007/s00109-007-0203-4
[34] Lukacs, K., Hosszufalusi, N., Dinya, E., Bakacs, M., Madacsy, L. and Panczel, P. (2012) The Type 2 Diabetes-Associated Variant in TCF7L2 Is Associated with Latent Autoimmune Diabetes in Adult Europeans and the Gene Effect Is Modified by Obesity: A Meta-Analysis and an Individual Study. Diabetologia, 55, 689-693.
http://dx.doi.org/10.1007/s00125-011-2378-z
[35] Gaulton, K.J., Nammo, T., Pasquali, L., Simon, J.M., Giresi, P.G., Fogarty, M.P., Panhuis, T.M., Mieczkowski, P., Secchi, A., Bosco, D., et al. (2010) A Map of Open Chromatin in Human Pancreatic Islets. Nature Genetics, 42, 255-259.
http://dx.doi.org/10.1038/ng.530
[36] Loos, R.J., Franks, P.W., Francis, R.W., Barroso, I., Gribble, F.M., Savage, D.B., Ong, K.K., O’Rahilly, S. and Wareham, N.J. (2007) TCF7L2 Polymorphisms Modulate Proinsulin Levels and Beta-Cell Function in a British Europid Population. Diabetes, 56, 1943-1947.
http://dx.doi.org/10.2337/db07-0055

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.