Polymorphic genetic markers and how they are associated with clinical and metabolic indicators of type 2 diabetes mellitus in the Kazakh population

Abstract

Background

Type 2 diabetes mellitus is a serious public health problem worldwide. The aim of the study was to analyze the relationship of eight polymorphic gene variants with the development of clinical-metabolic rates of type 2 diabetes mellitus inside Kazakh population.

Materials and methods

139 patients with type 2 diabetes mellitus and 100 patients in the control group were examined. Genotyping of polymorphisms of candidate genes was carried out on a next generation QuantStudio 12 K Flex unit.

Results

Gene TCF7L2 locus rs7901695 and rs7903146, gene KCNQ1 locus rs2237892, rs7756992, and gene CDKAL1 locus rs7754840 demonstrated statistically significant associations with glucose metabolism, lipid profile and body mass index (BMI) in type 2 DM inside the population. Statistically significant difference in anthropometric and biochemical measures of rs17584499, rs4712523 and rs163184 has not been revealed.

Conclusions

Genetic polymorphisms that influence pancreatic gland beta-cells insulin release and secretion associate with metabolic and anthropometric measures definitive for type 2 DM in Kazakh population.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Al-Safar H, Hassoun A, Almazrouei S, Kamal W, Afandi B, Rais N. Association of the genetic polymorphisms in transcription factor 7-like 2 and peroxisome proliferator-activated receptors- γ 2 with type 2 diabetes mellitus and its interaction with obesity status in Emirati population. J Diabetes Res. 2015;2015:1–8. https://doi.org/10.1155/2015/129695.

    Article  Google Scholar 

  2. 2.

    Al-Sinani S. Association of gene variants with susceptibility to type 2 diabetes among Omanis. World J Diabetes. 2015;6(2):358–66. https://doi.org/10.4239/wjd.v6.i2.358.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Benberin VV, Vochshenkova TA, Abildinova GZ, Borovikova AV, Nagimtayeva AA. Search for polymorphic variants of genes associated with type 2 diabetes in individuals of the Kazakh population. Revista TURISMO: Estudos e Práticas. 2020;2:1–10 Retrieved from http://natal.uern.br/periodicos/index.php/RTEP/article/view/1307.

    Google Scholar 

  4. 4.

    Boj SF, van Es JH, Huch M, Li VSW, José A, Hatzis P, et al. Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand. Cell. 2012;151(7):1595–607. https://doi.org/10.1016/j.cell.2012.10.053.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Chon SJ, Kim SY, Cho NR, Min DL, Hwang YJ, Mamura M. Association of variants in PPARγ2, IGF2BP2, and kcnq1 with a susceptibility to gestational diabetes mellitus in a Korean population. Yonsei Med J. 2013;54(2):352–7. https://doi.org/10.3349/ymj.2013.54.2.352.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Cook JP, Morris AP. Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility. Eur J Hum Genet. 2016;24(8):1175–80. https://doi.org/10.1038/ejhg.2016.17.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ding D, Chong S, Jalaludin B, Comino E, Bauman AE. Risk factors of incident type 2-diabetes mellitus over a 3-year follow-up: results from a large Australian sample. Diabetes Res Clin Pract. 2015;108(2):306–15. https://doi.org/10.1016/j.diabres.2015.02.002.

    Article  PubMed  Google Scholar 

  8. 8.

    El-Lebedy D, Ashmawy I. Common variants in TCF7L2 and CDKAL1 genes and risk of type 2 diabetes mellitus in Egyptians. J Genetic Engineering Biotechnol. 2016;14(2):247–51. https://doi.org/10.1016/j.jgeb.2016.10.004.

    Article  Google Scholar 

  9. 9.

    Global Lipids Genetics Consortium. Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013;45(11):1274–83. https://doi.org/10.1038/ng.2797.

    CAS  Article  Google Scholar 

  10. 10.

    Hiramoto M, Udagawa H, Ishibashi N, Takahashi E, Kaburagi Y, Miyazawa K, et al. A type 2 diabetes-associated SNP in KCNQ1 (rs163184) modulates the binding activity of the locus for Sp3 and Lsd1/Kdm1a, potentially affecting CDKN1C expression. Int J Mol Med. 2017;41(2):717–28. https://doi.org/10.3892/ijmm.2017.3273.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Hird TR, Young EH, Pirie FJ, Riha J, Esterhuizen TM, O’Leary B, et al. Study profile: the Durban diabetes study (DDS): a platform for chronic disease research. Global Health Epidemiol Genomics. 2016a;1:e2. https://doi.org/10.1017/gheg.2015.3.

    CAS  Article  Google Scholar 

  12. 12.

    Hird TR, Pirie FJ, Esterhuizen TM, O’Leary B, McCarthy MI, Young EH, et al. Burden of diabetes and first evidence for the utility of HbA1c for diagnosis and detection of diabetes in urban black south Africans: the Durban diabetes study. PLoS One. 2016b;11(8):e0161966. https://doi.org/10.1371/journal.pone.0161966.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Hwang J-Y, Sim X, Wu Y, Liang J, Tabara Y, Hu C, et al. Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in east Asians. Diabetes. 2015;64(1):291–8. https://doi.org/10.2337/db14-0563.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Imamura M, Takahashi A, Yamauchi T, Hara K, Yasuda K, Grarup N, et al. Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes. Nat Commun. 2016;7:10531. https://doi.org/10.1038/ncomms10531.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    International Diabetes Federation. IDF diabetes atlas. 5th ed. Brussels: IDF, Executive Office; 2011. Retrieved from https://www.idf.org/e-library/epidemiology-research/diabetes-atlas

    Google Scholar 

  16. 16.

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

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Islam MM. The practice of consanguineous marriage in Oman: prevalence, trends and determinants. J Biosoc Sci. 2012;44(5):571–94. https://doi.org/10.1017/S0021932012000016.

    Article  PubMed  Google Scholar 

  18. 18.

    Kaminska D, Kuulasmaa T, Venesmaa S, Kakela P, Vaittinen M, Pulkkinen L, et al. Adipose tissue TCF7L2 splicing is regulated by weight loss and associates with glucose and fatty acid metabolism. Diabetes. 2012;61(11):2807–13. https://doi.org/10.2337/db12-0239.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Klimentidis YC, Wineinger NE, Vazquez AI, de los Campos, G. Multiple metabolic genetic risk scores and type 2 diabetes risk in three racial/ethnic groups. J Clin Endocrinol Metabolism. 2014;99(9):E1814–8. https://doi.org/10.1210/jc.2014-1818.

    CAS  Article  Google Scholar 

  20. 20.

    Kommoju UJ, Maruda J, Kadarkarai S, Irgam K, Kotla JP, Velaga L, et al. No detectable association of IGF2BP2 and SLC30A8 genes with type 2 diabetes in the population of Hyderabad, India. Meta Gene. 2013;1:15–23. https://doi.org/10.1016/j.mgene.2013.09.003.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Kong X, Xing X, Hong J, Zhang X, Yang W. Genetic variants associated with lean and obese type 2 diabetes in a Han Chinese population: a case–control study. Medicine. 2016;95(23):e3841. https://doi.org/10.1097/MD.0000000000003841.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ministry of Health and Social Development of Kazakhstan, & Association of Endocrinologists of Kazakhstan. (2016). Consensus on the diagnosis and treatment of diabetes (issue 4). Almaty.

    Google Scholar 

  23. 23.

    Namvaran F, Azarpira N, Rahimi-Moghaddam P, Dabbaghmanesh MH. Polymorphism of peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala in the Iranian population: relation with insulin resistance and response to treatment with pioglitazone in type 2 diabetes. Eur J Pharmacol. 2011;671(1–3):1–6. https://doi.org/10.1016/j.ejphar.2011.09.158.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Nemr R, Almawi AW, Echtay A, Sater MS, Daher HS, Almawi WY. Replication study of common variants in CDKAL1 and CDKN2A/2B genes associated with type 2 diabetes in Lebanese Arab population. Diabetes Res Clin Pract. 2012;95(2):e37–40. https://doi.org/10.1016/j.diabres.2011.11.002.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Ng MCY, Shriner D, Chen BH, Li J, Chen W-M, Guo X, et al. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLoS Genet. 2014;10(8):e1004517. https://doi.org/10.1371/journal.pgen.1004517.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Nikitin AG, Potapov VY, Brovkina OI, Koksharova EO, Khodyrev DS, Philippov YI, et al. Association of polymorphic markers of genes FTO , KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population. PeerJ. 2017;5:e3414. https://doi.org/10.7717/peerj.3414.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Noordam R, Zwetsloot CPA, de Mutsert R, Mook-Kanamori DO, Lamb HJ, de Roos A, et al. Interrelationship of the rs7903146 TCF7L2 gene variant with measures of glucose metabolism and adiposity: the NEO study. Nutr Metab Cardiovasc Dis. 2018;28(2):150–7. https://doi.org/10.1016/j.numecd.2017.10.012.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Palit SP, Patel R, Jadeja SD, Rathwa N, Mahajan A, Ramachandran AV, et al. A genetic analysis identifies a haplotype at adiponectin locus: association with obesity and type 2 diabetes. Sci Rep. 2020;10(1):2904. https://doi.org/10.1038/s41598-020-59845-z.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Pei Q, Huang Q, Yang G, Zhao Y, Yin J, Song M, et al. PPAR-γ2 and PTPRD gene polymorphisms influence type 2 diabetes patients’ response to pioglitazone in China. Acta Pharmacol Sin. 2013;34(2):255–61. https://doi.org/10.1038/aps.2012.144.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    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 Metabolism J. 2015;39(6):512–7. https://doi.org/10.4093/dmj.2015.39.6.512.

    Article  Google Scholar 

  31. 31.

    Qi Q, Stilp AM, Sofer T, Moon J-Y, Hidalgo B, Szpiro AA, et al. Genetics of type 2 diabetes in U.S. Hispanic/Latino individuals: results from the hispanic community health study/study of Latinos (HCHS/SOL). Diabetes. 2017;66(5):1419–25. https://doi.org/10.2337/db16-1150.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Rathwa N, Patel R, Palit SP, Ramachandran AV, Begum R. Genetic variants of resistin and its plasma levels: association with obesity and dyslipidemia related to type 2 diabetes susceptibility. Genomics. 2019;111(4):980–5. https://doi.org/10.1016/j.ygeno.2018.06.005.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Roglic G, World Health Organization, editors. Global report on diabetes. Geneva: World Health Organization; 2016.

    Google Scholar 

  34. 34.

    dos Santos MCF, Anderson CP, Neschen S, Zumbrennen-Bullough KB, Romney SJ, Kahle-Stephan M, et al. Irp2 regulates insulin production through iron-mediated Cdkal1-catalyzed tRNA modification. Nat Commun. 2020;11(1):296. https://doi.org/10.1038/s41467-019-14004-5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Scott RA, Scott LJ, Mägi R, Marullo L, Gaulton KJ, Kaakinen M, et al. An expanded genome-wide association study of type 2 diabetes in Europeans. Diabetes. 2017;66(11):2888–902. https://doi.org/10.2337/db16-1253.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Srinivasan S, Kaur V, Chamarthi B, Littleton KR, Chen L, Manning AK, et al. TCF7L2 genetic variation augments incretin resistance and influences response to a sulfonylurea and metformin: the study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH). Diabetes Care. 2018;41(3):554–61. https://doi.org/10.2337/dc17-1386.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Sun Q, Song K, Shen X, Cai Y. The association between kcnq1 gene polymorphism and type 2 diabetes risk: a meta-analysis. PLoS One. 2012;7(11):e48578. https://doi.org/10.1371/journal.pone.0048578.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Sun X-F, Xiao X-H, Zhang Z-X, Liu Y, Xu T, Zhu X-L, et al. Positive association between type 2 diabetes risk alleles near CDKAL1 and reduced birthweight in Chinese Han individuals. Chin Med J. 2015;128(14):1873–8. https://doi.org/10.4103/0366-6999 160489.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Temelkova-Kurktschiev T, Stefanov T. Lifestyle and genetics in obesity and type 2 diabetes. Exp Clin Endocrinol Diabetes. 2012;120(01):1–6. https://doi.org/10.1055/s-0031-1285832.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526(7571):68–74. https://doi.org/10.1038/nature15393.

    CAS  Article  PubMed Central  Google Scholar 

  41. 41.

    Wheeler E, Barroso I. Genome-wide association studies and type 2 diabetes. Briefings Functional Genomics. 2011;10(2):52–60. https://doi.org/10.1093/bfgp/elr008.

    CAS  Article  Google Scholar 

  42. 42.

    WHO Department of Noncommunicable Disease Management. (2003). Screening for type 2 diabetes: Report of a World Health Organization and International Diabetes Federation meeting (No. WHO/NMH/MNC/CRA/03.1). Retrieved from World Health Organization website: https://apps.who.int/iris/handle/10665/68614

  43. 43.

    Xia Q, Deliard S, Yuan C-X, Johnson ME, Grant SF. Characterization of the transcriptional machinery bound across the widely presumed type 2 diabetes causal variant, rs7903146, within TCF7L2. Eur J Hum Genet. 2015;23(1):103–9. https://doi.org/10.1038/ejhg.2014.48.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Almagul A. Nagimtayeva.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Benberin, V.V., Vochshenkova, T.A., Abildinova, G.Z. et al. Polymorphic genetic markers and how they are associated with clinical and metabolic indicators of type 2 diabetes mellitus in the Kazakh population. J Diabetes Metab Disord (2021). https://doi.org/10.1007/s40200-020-00720-z

Download citation

Keywords

  • T2DM (type 2 diabetes mellitus)
  • SNP (single nucleotide polymorphism)
  • Genetic typing
  • Genetic predisposition
  • Gene