Association of TCF7L2 Gene Polymorphism With Non Obesetype 2 Diabetes Mellitus in Javanese Population

Ari Yuniastuti; R Susanti; Nugrahaningsih Nugrahaningsih; Rahmatika Saputri R

doi:10.26877/bioma.v12i2.15365

Association of TCF7L2 Gene Polymorphism With Non Obesetype 2 Diabetes Mellitus in Javanese Population

Ari Yuniastuti, R Susanti, Nugrahaningsih Nugrahaningsih, Rahmatika Saputri R

Abstract

Type 2 diabetes is characterized by insulin deficiency due to inadequate insulin secretion or decreased tissue response to insulin at one or more points. Three important factors that influence the pathogenesis of type 2 DM are individual factors or ethnic genetics, factors of pancreatic β cell damage and insulin resistance factors. The TCF7L2 gene is a gene that codes for TCF7L2 protein, a group of proteins that act as transcription factors in the Wnt signal pathway. TCF7L2 gene polymorphism occurs when cytosine is replaced with thymine in the intron 3 position in wild-type due to alternative splicing.The purpose study was to determine the frequency of TCF7L2 gene polymorphism in Javanese type 2 non-obese DM patients in Semarang. Detection of TCF7L2 gene polymorphism was carried out on 49 people with type 2 non-obese DM patients and 38 people not with type 2 DM using the PCR-RFLP method. The restriction enzyme used is Rsa1. The allele frequency of TCF7L2 gene polymorphism was analyzed by Chi-square and analysis of sample characteristics was carried out with Odds Ratio. The results showed that there were significant differences in the allele frequency of TCF7L2 gene polymorphism and in the characteristics of age, KGD and systole between case subjects and control subjects. From this study it was concluded that TCF7L2 gene polymorphism is associated with the type 2 DM through interactions between genetic factors (T allele) and life style.

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References

Alibegovic, A. C., Sonne M. P., Hojbjerre L., Hansen T., Pedersen O. & Hall, G. 2010. The T-Allele Of TCF7L2 rs7903146 Associates With a Reduced Compensation Of Insulin Secretion For Insulin Resistance Induced by 9 Days Of Bed Rest. Diabetes. 59(4): 836-843.

Balasubramanyam, M. 2007. TCF7L2 and diabetes – A transcription gene with prescription hope?. Current Science. 5(93):613-615.

Cauchi S.,Younes E. A., Hélène C., Christian D., Franz K., Raimund W., Chakib N., Wolfgang P., Mohamed C. D. M. & Philippe F.2007. TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis. Journal of Moleculer Medicine.85(7):777–782.

Chang, C. Y., Chang, J. T., Jiang, D. Y., Kuo, S. S., Lee, C. K., Chiu, C. K. & Chuang L, M. 2007. Association Study of the Genetic Polymorphism of the Transcription Factor 7-like 2 (TCF7L2) Gene and Type 2 Diabetes in the Chinese Population. Diabetes. 56(10):2631-2637.

Dinas Kesehatan Provinsi Jawa Tengah. 2017. Profil Kesehatan Provinsi Jawa Tengah Tahun 2017. Semarang.

Grant, S. F. A., Thorleifsson G., Reynisdottir I., Benediktsson R., Manolescu A., Sainz J., Helgason A., Stefansso H., Emilsson V., Helgadottir A., Styrkarsdottir U., Magnusson K. P., Walters G. B., Palsdottir E., Jonsdottir T., Gudmundsdottir T., Gylfason A., Saemundsdottir J., Wilensky R. L., Reilly M. P., Rader D. J., Bagger Y., Christiansen C., Gudnason V., Sigurdsson G., Thorsteinsdottir U., Gulcher J. R., Kong A. & Stefansson K. 2006. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nature Genetics.38(3):320-323.

Gloyn, A. L., Matthias B. & Patrick R. 2009. Type 2 Diabetes Susceptibility Gene TCF7L2 and Its Role in β-Cell Function. Diabetes. 58(3):800-802.

Groves C. J., Eleftheria Z., Jayne M., Timothy M. F., Michael N. W., Nigel W. R., Graham A. H., Mark W., Steven W., Andrew T. H. & Mark I. M.2006. Association analysis of 6,736 U.K. subjects provides replication and conﬁrms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individualrisk.Diabetes.55(9):2640–2644.

International Diabetes Federation. IDF Diabetes Atlas 8th ed. India: Prof. Shaukat Sadikot

Isganaitis E. & Lustig R. H. 2005. Fast food, central nervous system insulin resistance and obesity.American Heart Association, Inc (Brief Reviewer).25(1):2451-2462.

Jin, T. 2008. The Wnt Signalling pathway and diabetes mellitus. Diabetologia. 51(2):1771-1780.

Jyothi, K. U., Maruda J., Kadarkarai S. S., Kotla J. P., Irgam K., Velaga L. & Battini M. R. 2013. Association of TCF7L2 Gene Polymorphisms with T2DM in the Population of Hyderabad, India. Plos One. 8(4):1-7.

Liao, P. Y.& Kelvin H. L. 2010. From SNPs to functional polymorphism-the insight into biotechnology application. Biochemical Engineering Journal. 49(2): 149-158.

Kurniawaty, E. & Bella Y. 2016.Faktor-faktor yang berhubungan dengan kejadian Diabetes Mellitus Tipe 2.Mojority. 5(2):27-31.

Mainous G., Rebecca J., Ara J. & Stephen D. A.2016. Prevalence of Prediabetes and Abdominal Obesity Among Healthy-Weight Adults: 18-Year Trend.Annals Of Family Medicine.14(4):304-310.

McCarthy, M. 2010. Genomics, type 2 diabetes and obesity. New England Journal of Medicine. 363(24):2339-2350.

Meloni, A. R., Deyoung M. B., Lowe C., & Parkes D. G. 2013. GLP-1 Receptor Activated Insulin Secretion From Pancreatic β-cells: Mechanism and Glucose Dependence. Diabetic Obes and Metabolism. 15(3): 15-27.

Miyake K., Yukio H., Kazuo H., Kazuki Y., Haruhiko O., Hiroto F., Yushi H., Kazuya Y., Yoshinori H., Yoshitomo O., Naoka I., Yasuhiko I., Yuichiro Y., Yutaka S., Hiroshi M., Atsunori K., Ken Y., Katsushi T., Jun T., Hideichi M., Kaishio N., Takashi K. & Masato K.2008.Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects.The Japan Society of Human Genetics and Springer.53(2):174–180.

Nadyah A. 2013. Gambaran Faktor Resiko Pasien Diabetes Tipe II di Poliklinik Endokrin RSU Dr. R.D. Kandou Manado. Jurnal e-Biomedik. 1(1):45-9.

Nanfa, D., Sobngwi E., Tiedeu B. A., Noubiap J. J. N., Donfack O. S., Mofo E. P. M., Fokeng M.G., Metsadjio A. N., Ngwa E. N., Fosso P. P., Djahmeni E., Dadjeu R. D., Evehe M. S., Aminkeng F., Mbacham W. F. & Mbanya J. C. 2015. Association between the TCF7L2 rs12255372 (G/T) gene polymorphism and type 2 diabetes Mellitusin a Cameroonian population: a pilot study. Clinical and Translational Medicine. 4(17):2-5.

Pardede, Tami E., Dani R. & Erwin C. 2017.Gambaran Pengendalian Diabetes Melitus Berdasarkan Parameter Indeks Massa Tubuh dan Tekanan Darah di Poli Rawat Jalan Penyakit Dalam RSUD Arifin Achmad Pekanbaru.Jurnal Online Mahasiswa Fk. 4(1):1-14.

Perkeni. 2011. Konsensus Pengelolaan dan Pencegahan Diabetes Mellitus Tipe 2 di Indonesia, (online).

Prokunina, O. L., Lee M. K., Eric E. S. & Francis S. C. 2009.Alternative Splicing of TCF7L2 Gene in Omental and Subcutaneous Adipose Tissue and Risk of Type 2 Diabetes.Plos One.4(9):1-8.

Sale M. M., Shelly G. S., Josyf C. M., Keith L. K., Carld D. L., Tennille S. L., Pamela J. H., Donald W. B., Stephen S. R. & Barry I. F.2007.Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy.Diabetes.56(10):2638–2642.

Savic, D., Ye H., Aneas I., Park S., Bell I. G.&Nobrega A. M., 2011. Alteration in TCF7L2 expression define its role as a key regulator of glucose metabolsm. Genetics Research. 21(9):1417-1425.

Scott L. J., Lori L. B., Cristen J. W., Andrew G. S., Anne U. J., Narisu, William J. T., Richard N. B., Karen L. M., Francis S. C. & Michael B.2006.Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample.Diabetes.55(9):2 z649–2653.

Seino, Y., Kishio N., Naoko T.,Takashi K., Atsunori K., Eiichi A., Chikako I., Nobuya I., Yasuhiko I., Masato K., Toshiaki H., Masakazu H. & Kohjiro U. 2010. Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus.Journal of Diabetes Investigation. 1(5):212-228.

Shuldiner A.R., Yang R. & Gong D.W.2001.Resistin, obesity, and insulin resistance the emerging role of the adipocyte as an endocrine organ.New England Journal Of Medicine.345(18):1345-1346.

Trisnawati S. K. & Soedijono S.2013. Faktor Risiko Kejadian Diabetes Melitus Tipe II Di Puskesmas Kecamatan Cengkareng Jakarta Barat Tahun 2012.Jurnal Ilmiah Kesehatan.5(1):6-11.

Yu, J., Steck A. K., Babu S., Yu L., Miao D. & McFann K. 2009. Single Nucleotide Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphisms in Antiislet Autoantibody-Negative Patients at Onset of Diabetes. Endocrine Care. 94(2):504-510.

Zeggini E. 2007. A new era for type 2 diabetes genetics.Diabetic Medicine. 24(11):1181-1186.

DOI: https://doi.org/10.26877/bioma.v12i2.15365