Single Nucleotide Polymorphism at rs7903146 of Transcription Factor 7-like 2 gene Among Subjects with Type 2 Diabetes Mellitus in Myanmar

Authors

  • Sagawah Phu Department of Biochemistry, University of Medicine Taunggyi https://orcid.org/0000-0002-1985-1564
  • Aye Thida University of Medicine 2, Yangon, Myanmar https://orcid.org/0000-0002-6390-8193
  • Kyu Kyu Maung University of Medicine 1, Yangon, Myanmar
  • Tet Tun Chit East Yangon General Hospital, Yangon, Myanmar

DOI:

https://doi.org/10.15605/jafes.037.S2

Keywords:

TCF7L2, SNP, Myanmar

Abstract

Objectives. To investigate the association between the single nucleotide polymorphism (SNP) rs7903146 in the transcription factor 7-like 2 (TCF7L2) gene and type 2 diabetes mellitus (T2DM) and to examine the impact of this variant on pancreatic beta-cell function in the Myanmar population.

Methodology.  A case-control study was undertaken in 100 subjects with T2DM and 113 controls. The SNP rs7903146 was genotyped using the allele-specific polymerase chain reaction method. Plasma glucose and serum insulin levels were determined using the enzymatic colorimetric method and ELISA respectively. Beta-cell function was calculated by the HOMA-β formula.

Results. The frequencies of carrier genotypes (CT and TT) were higher in subjects with T2DM than in controls. The minor T alleles of rs7903146 were found to statistically increase type 2 diabetes risk than the C allele with an allelic odds ratio of 2.07 (95% CI 1.39-3.09, p=0.0004). The mean HOMA-β level of the group with non-carrier genotype (CC) was significantly higher than that of the groups with carrier genotypes (CT and TT) in subjects with T2DM and controls with a p-value of 0.0003 and less than 0.0001, respectively.

Conclusion. The rs7903146 variant of the TCF7L2 gene was found to be associated with T2DM and low β-cell function among Myanmar subjects.

Downloads

Download data is not yet available.

Author Biographies

Aye Thida, University of Medicine 2, Yangon, Myanmar

Professor and Head, Department of Medical Education

Kyu Kyu Maung, University of Medicine 1, Yangon, Myanmar

Professor and Head, Department of Biochemistry

Tet Tun Chit, East Yangon General Hospital, Yangon, Myanmar

Senior Consultant Physician, Department of Medicine

References

Kahn CR. Banting lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes. 1994; 43(8):1066-84. https://pubmed.ncbi.nlm.nih.gov/8039601. https://doi.org/10.2337/diab.43.8.1066.

Suzuki K, Akiyama M, Ishigaki K, et al. Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population. Nat Genet. 2019;51(3): 379-86. https://pubmed.ncbi.nlm.nih.gov/30718926. https://doi.org/10.1038/s41588-018-0332-4.

Hayashi T, Iwamoto Y, Kaku K, Hirose H, Maeda S. Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population. Diabetologia. 2007;50(5):980-4. https://pubmed.ncbi.nlm.nih.gov/17340123. https://doi.org/10.1007/s00125-007-0618-z.

Ren Q, Han XY, Wang F, et al. Exon sequencing and association analysis of polymorphisms in TCF7L2 with type 2 diabetes in a Chinese population. Diabetologia. 2008;51(7):1146-52. https://pubmed.ncbi.nlm.nih.gov/18493736. https://doi.org/10.1007/s00125-008-1039-3.

Dabelea D, Dolon LM, Agostino Jr RD, et al. Association testing of TCF7L2 polymorphisms with type 2 diabetes in multi-ethnic youth. Diabetologia; 2011; 54(3):535-9. https://pubmed.ncbi.nlm.nih.gov/21109996. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766323. https://doi.org/10.1007/s00125-010-1982-7.

Duval A, Rolland S, Tubacher E, Bui H, Thomas G, Hamelin R. The human T –cell transcriptional factor-4 gene: Structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines. Cancer Res. 2000; 60(14):3872-9. https://pubmed.ncbi.nlm.nih.gov/10919662.

Grant SFA, Thorleifsson G, Reynisdottir I, et al. Variant of transcriptional factor 7- like 2 gene confers risk of type 2 diabetes. Nat Genet. 2006; 38(3):320-3. https://pubmed.ncbi.nlm.nih.gov/16415884. https://doi.org/10.1038/ng1732.

Peng S, Zhu Y, Lü B, Xu F, Li X, and Lai M. TCF7L2 gene polymorphisms and type 2 diabetes risk: A comprehensive and updated meta-analysis involving 121 174 subjects. Mutagenesis. 2013; 28(1): 25-37. https://pubmed.ncbi.nlm.nih.gov/23188737. https://doi.org/10.1093/mutage/ges048.

Zhou Y, Park SY, Su J, et al. TCF7L2 is a master regulator of insulin production and processing. Hum Mol Genet. 2014;23(24):6419–31. https://pubmed.ncbi.nlm.nih.gov/25015099. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240194. https//doi.org/10.1093/ hmg/ddu359.

Cropano C, Santoro N, Groop L, et al. The rs7903146 variant in the TCF7L2 gene increases the risk of prediabetes/type 2 diabetes in obese adolescents by impairing β-cell function and hepatic insulin sensitivity. Diabetes Care. 2017;40(8):1082-9. https://pubmed.ncbi.nlm.nih.gov/28611053. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521977. https://doi.org/10.2337/dc17-0290.

Schäfer SA, Tschritter O, Machicao F, et al. Impaired glucagon-like peptide-1-induced insulin secretion in carrier of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia. 2007;50(12):2443-50. https://pubmed.ncbi.nlm.nih.gov/17661009. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063563. https://doi.org/10.1007/s00125-007-0753-6.

Prestwich TC, Macdouglad OA. Wnt/ beta catenin signaling in adipogenesis and metabolism. Curr Opin Cell Biol. 2007;19(6):612-7. https://pubmed.ncbi.nlm.nih.gov/17997088. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709272. https://doi.org/10.1016/j.ceb.2007.09.014.

Rulifson IC, Karnik SK, Heiser PW, et al. Wnt signaling regulates pancreatic beta cell proliferation. Proc Natl Acad Sci USA. 2007; 104(15):6247-52. https://pubmed.ncbi.nlm.nih.gov/17404238. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847455. https://doi.org/10.1073/pnas.0701509104.

Barra GB, Dutra LAS, Watanabe SC, et al. Association of the rs7903146 single nucleotide polymorphism at the transcriptional factor 7-like 2 (TCF7L2) locus with type 2 diabetes in Brazilian subjects. Arq Bras Endocrinol Metabol. 2012; 56(8): 479-84. https://pubmed.ncbi.nlm.nih.gov/23295285. https://doi.org/10.10590/s0004-27302012000800003.

Yi F, Brubaker PL, Jin T. TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem. 2005; 280(2): 1457-64. https://pubmed.ncbi.nlm.nih.gov/15525634. https://doi.org/10.1074/jbc.M411487200.

Lyssenko V, Lupi R, Marchetti P, et al. Mechanisms by which common variants in TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest. 2007;117(8):2155-63. https://pubmed.ncbi.nlm.nih.gov/17671651. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934596. https://doi.org/10.1172/JCI30706.

Ferreira MC, da Silva MER, Fukui RT, Arruda-Marques MdC, Azhar S, Dos Santos RF. Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes. Diabetol Metab Syndr. 2019; 11:10-19. https://pubmed.ncbi.nlm.nih.gov/ 30700996. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347826. https://doi.org/10.1186/s13098-019-0401-6.

World Health Organization and International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: Report of a WHO/IDF consultation. Geneva, Switzerland: World Health Organization, 2006. http://apps.who.int/iris/handle/10665/43588. Accessed December 5, 2010.

Moczulski D, Gawlik B, August R, Strojek K and Grzeszczak W. TCF7L2 gene is associated with type 2 diabetes in Polish population. Exp Clinic Diabetologia, 2007;7(2):109-11.

Thabane L. Sample size determination in clinical trials. HRM-733 Class-Notes. https://www.scribd.com/document/358495328/Thabane-L-Sample-Size-Determination-in-Clinical-Trials-2004-pdf. Accessed by January 20, 2010.

Dutra LAS, Costa PGG, Velasco LFR, Amato AA, Barra GBB. Allele-specific PCR assay to genotype SNP rs7903146 in TCF7L2 gene for rapid screening of diabetes susceptibility. Arg Bras Endocrinol Metabol. 2008; 52(8):1362-6. https://pubmed.ncbi.nlm.nih.gov/19169495. https://doi.org/10.1590/s0004-27302008000800026.

Mayans S, Lockovic K, Lindgren P, et al. TCF7L2 polymorphisms are associated with type 2 diabetes in northern Sweden. Eur J Hum Genet. 2007;15(3):342-6. https://pubmed.ncbi.nlm.nih.gov/17245407. https://doi.org/10.1038/sj.ejhg.5201773.

Cauchi S, Meyre D, Dina C, et al. Transcription factor TCF7L2 genetic study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes. Diabetes. 2006; 55(10):2903-8. https://pubmed.ncbi.nlm.nih.gov/17003360. https://doi.org/10.2337.db06-0474.

Marquezine GF, Pereira AC, Sousa AGP, Mill JG, Hued WA, Krieger JE. TCF7L2 variant genotypes and type 2 diabetes risk in Brazil: Significant association, but not a significant tool for risk stratification in the general population. BMC Med Genet. 2008; 9: 106. https://pubmed.ncbi.nlm.nih.gov/19055834. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632659. https://doi.org/10.1186/1471-2350-9-106.

Chandak GR, Janipalli CS, Bhaskar S, et al. Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Diabetologia, 2007; 50(1):63-7. https://pubmed.ncbi.nlm.nih.gov/17093941. https://doi.org/10.1007/s00125-006-0502-2.

Bahaaeldin AM, Seif AA, Hamed AI, Kabiel WAY. Transcription factors 7-like 2 (TCF7L2) rs 7903146 (C/T) polymorphism in patients with type 2 diabetes mellitus. Dubai Diabetes Endocrinol J. 2020;26:112-8. https://doi.org/10.1159/000509756.

Elhourch S, Arrouchi H, Mekkaoui N, et al. Significant association of polymorphisms in the TCF7L2 gene with a higher risk of type 2 diabetes in a Moroccan population. J Pers Med. 2021;11(6):461. https://pubmed.ncbi.nlm.nih.gov/34073870. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225140. https://doi.org/10.3390/jpm11060461.

Ng MCY, Tam CHT, Lam VKL, So WY, Ma RCW, Chan JCN. Replication and identification of novel variants at TCF7L2 associated with type 2 diabetes in Hong Kong Chinese. J Clin Endocrinol Metab. 2007;92(9):3733-7. https://pubmed.ncbi.nlm.nih.gov/17609304. https://doi.org/10.1210/jc.2007-0849.

Pourahmadi M, Erfanian S, Moradzadeh M, Jahromi AS. Non-association between rs7903146 and rs12255372 polymorphisms in transcription factor 7-like 2 gene and type 2 diabetes mellitus in Jahrom City, Iran. Diabetes Metab J. 2015; 39(6): 512-7. https://pubmed.ncbi.nlm.nih.gov/26616591. https://doi.org/10.4093/dmj.2015.39.6.512.

Mandour I, Darwish R, Fayez R, Naguib M, El-Sayegh S. TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus, a pilot study.

Biomedical Pharmacol J. 2018; 11(2): 1043-9. https://doi.org/10.13005/bpj/1465.

Meier JJ, Bonadonna RC. Role of reduced β-cell mass versus impaired β-cell function in the pathogenesis of type 2 diabetes. Diabetes Care. 2013; 36(2):113-9. https://pubmed.ncbi.nlm.nih.gov/23882035. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920783. https://doi.org/10.2337.dcS13-2008.

Loos Ruth JF, Franks PW, Francis RW, Barroso I, Gribble FM, Savage DB. TCF7L2 polymorphisms modulate proinsulin level and beta-cell function in a British Europid population. Diabetes. 2007;56(7):1943-7. https://pubmed.ncbi.nlm.nih.gov/17416797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668957. https://doi.org/10.2337/db07-0055.

Papadopoulou S, Edlund H. Attenuated Wnt signaling perturbs pancreatic growth but not pancreatic function. Diabetes. 2005; 54(10): 2844-51. https://pubmed.ncbi.nlm.nih.gov/16186384. https://doi.org/10.2337.diabetes.54.10.2844.

Takamoto I, Kubota N, Nakaya K, et al. TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis by regulating beta cell mass. Diabetologia. 2014; 57(3): 542–53. https://pubmed.ncbi.nlm.nih.gov/24317852. https://doi.org/10.1007/s00125-013-3131-6

Shu L, Matveyenko A, Kerr-Conte J, Cho JH, McIntosh CHS, Maedler K. Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP and GLP-1 receptors and impaired beta cell function. Hum Mol Genet. 2009;18(13):2388-2399. https://pubmed.ncbi.nlm.nih.gov/19386626. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722186. https://doi.org/10.1093/hmg/ddp178.

da Silva Xavier G, Loder MK, McDonald A, et al. TCF7L2 regulates late events in insulin secretion from pancreatic islet beta cells. Diabetes. 2009;58(4):894-905. https://pubmed.ncbi.nlm.nih.gov/19168596. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661588. https://doi.org/10.2337/db08-1187.

Downloads

Published

2021-12-03

How to Cite

Sagawah Phu, Thida, A., Maung, K. K., & Chit, T. T. (2021). Single Nucleotide Polymorphism at rs7903146 of Transcription Factor 7-like 2 gene Among Subjects with Type 2 Diabetes Mellitus in Myanmar. Journal of the ASEAN Federation of Endocrine Societies, 38(S1), 41–47. https://doi.org/10.15605/jafes.037.S2