Insulin-like Growth Factor-2 Binding Protein-2 Gene Polymorphisms in Iraqi Patients with Type 2 Diabetes Mellitus

Authors

  • Zubaida Falih Department of Clinical Laboratory Sciences, Faculty of Pharmacy, University of Kufa, Kufa, Iraq https://orcid.org/0000-0003-3784-4437
  • Bayadir Ali Wannas Khodair Department of Physiology, Faculty of Veterinary Medicine, University of Kufa, Kufa, Iraq
  • Noaman Ibadi Mohammed Department of Physiology, Faculty of Veterinary Medicine, University of Kufa, Kufa, Iraq
  • Tahseen Kadhem Mohammed Department of Clinical Laboratory Sciences, Faculty of Pharmacy, University of Kufa, Kufa, Iraq

DOI:

https://doi.org/10.3889/oamjms.2022.9754

Keywords:

Polymorphism, T2DM, IGF2BP2 gene, RFLP-PCR

Abstract

Background: Diabetes mellitus type2 (T2DM) represent a hyperglycemia causing metabolic disease which exists in the peripheral tissues due to incomplete pancreatic insulin secretion or insulin resistance. IGF2BP2 is a protein that is involved in embryogenesis and pancreatic development. Genetic association researches had suggested that the single nucleotide polymorphisms (SNP) spanning IGF2BP2 gene are associated with the progression as well as development of the T2DM.

Aim: This study aims to evaluate the association of IGF2BP2 gene polymorphisms (rs4402960 & rs1470579) with T2DM in a sample of Iraqi individuals.

Methods: A case-control study has been conducted on 800 participants, they were divided to two equal groups, which are a healthy control group (400) and type 2 diabetic patients (400). Fast blood sugar (FBS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and HbA1c] measured suitable for both participant groups. IGF2BP2 gene has been genotyped for polymorphisms; rs4402960 and rs1470579 by using the PCR-RFLP technique.

Results: There is significant changes in the biochemical parameters in patients group when compared to the control group.The SNP rs4402960 show minor allele frequency of T allele considerably different between the two participating groups (p 0.0013) with 33.6 % in T2DM group. Homo-variant TT shows a significant p <0.0001) odd ratio (4.5) as codominant type. Similarly, dominant and recessive models exert significant (0.02 & <0.0001 respectively) adjusted odd ratio (1.45 & 4.14 respectively). The rs1470579 SNP show a significant (0.024) risk (1.28) of C allele in the patients group than in A allele. The CC genotype in codominant and recessive models show significant (0.03) odd ratio differences (2.03 & 1.96 respectively. The rs1470579 SNP exerts significant differences as codominant model in biochemical features of BMI, FBG, Tgs, VLDL-C, insulin and HOMA-IR. The study power of rs4402960 is 69.5% and rs1470579 is 34.1%.

Conclusion: This study confirmed the association of rs4402960 as codominant, dominant and recessive with T2DM significantly. However, rs1470579 is associate as recessive model with T2DM in Iraqi population. 

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References

Wondmkun YT. Obesity, insulin resistance, and type 2 diabetes: Associations and therapeutic implications. Diabetes Metab Syndr Obes. 2020;13:3611-6. https://doi.org/10.2147/DMSO.S275898 PMid:33116712 DOI: https://doi.org/10.2147/DMSO.S275898

Cheng F, Liu L, Zhang H, Zhu Y, Li X, Li H. Association of IL-16 gene polymorphisms with the risk of developing type 2 diabetes mellitus in the Chinese Han population. Biosci Rep. 2019;39(8):BSR20190821. https://doi.org/10.1042/BSR20190821 PMid:31375554 DOI: https://doi.org/10.1042/BSR20190821

Christiansen J, Kolte AM, Hansen TV, Nielsen FC. IGF2 mRNA-binding protein 2: Biological function and putative role in type 2 diabetes. J Mol Endocrinol. 2009;43(5):187-95. https://doi.org/10.1677/JME-09-0016 PMid:19429674 DOI: https://doi.org/10.1677/JME-09-0016

Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol Cell Biol. 1999;19(2):1262-70. https://doi.org/10.1128/mcb.19.2.1262 PMid:9891060 DOI: https://doi.org/10.1128/MCB.19.2.1262

Zhang JY, Chan EK, Peng XX, Tan EM. A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma. J Exp Med. 1999;189(7):1101-10. https://doi.org/10.1084/jem.189.7.1101 PMid:10190901 DOI: https://doi.org/10.1084/jem.189.7.1101

Cao J, Yan W, Ma X, Huang H, Yan H. Insulin-like growth factor 2 mRNA-binding protein 2-a potential link between type 2 diabetes mellitus and cancer. J Clin Endocrinol Metab. 2021;106(10):2807-18. https://doi.org/10.1210/clinem/dgab391 PMid:34061963 DOI: https://doi.org/10.1210/clinem/dgab391

Cao J, Mu Q, Huang H. The roles of insulin-like growth factor 2 mRNA-binding protein 2 in cancer and cancer stem cells. Stem Cells Int. 2018;2018:4217259. https://doi.org/10.1155/2018/4217259 PMid:29736175 DOI: https://doi.org/10.1155/2018/4217259

Yaniv K, Yisraeli JK. The involvement of a conserved family of RNA binding proteins in embryonic development and carcinogenesis. Gene. 2002;287(1-2):49-54. https://doi.org/10.1016/S0378-1119(01)00866-6 PMid:11992722 DOI: https://doi.org/10.1016/S0378-1119(01)00866-6

Boudoukha S, Cuvellier S, Polesskaya A. Role of the RNA-binding protein IMP-2 in muscle cell motility. Mol Cell Biol. 2010;30(24):5710-25. https://doi.org/10.1128/mcb.00665-10 PMid:20956565 DOI: https://doi.org/10.1128/MCB.00665-10

Esparza-Moltó PB, Cuezva JM. Reprogramming oxidative phosphorylation in cancer: A role for rna-binding proteins. Antioxidants Redox Signal. 2020;33(13):927-45. https://doi.org/10.1089/ars.2019.7988 PMid:31910046 DOI: https://doi.org/10.1089/ars.2019.7988

Janiszewska M, Suvà M, Riggi N, Houtkooper R, Auwerx J, Clément-Schatlo V, et al. Imp2 controls oxidative phosphorylation and is crucial for preservin glioblastoma cancer stem cells. Genes Dev. 2012;26(17):1926-44. https://doi.org/10.1101/gad.188292.112 PMid:22899010 DOI: https://doi.org/10.1101/gad.188292.112

Dai N, Zhao L, Wrighting D, Krämer D, Majithia A, Wang Y, et al. IGF2BP2/IMP2-deficient mice resist obesity through enhanced translation of Ucp1 mRNA and other mRNAs encoding mitochondrial proteins. Cell Metab. 2015;21(4):609-21. https://doi.org/10.1016/j.cmet.2015.03.006 PMid:25863250 DOI: https://doi.org/10.1016/j.cmet.2015.03.006

Sanghera D, Ortega L, Han S, Singh J, Ralhan S, Wander G, et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet. 2008;9:1-9. https://doi.org/10.1186/1471-2350-9-59 PMid:18598350 DOI: https://doi.org/10.1186/1471-2350-9-59

Stancáková A, Kuulasmaa T, Paananen J, Jackson AU, Bonnycastle LL, Collins FS, et al. Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes. 2009;58(9):2129-36. https://doi.org/10.2337/db09-0117 PMid:19502414 DOI: https://doi.org/10.2337/db09-0117

Mohammed A, Nagwan A, Amany Y, Fathalla M, Abdelraouf M. Insulin-like growth factor 2 binding protein 2 gene polymorphism in Egyptian patients with type 2 diabetes. Egypt J Biochem Mol Biol. 2018;36(1-2):35-48. https://doi.org/10.21608/ejb.2018.19873 DOI: https://doi.org/10.21608/ejb.2018.19873

Tarnowski M, Bujak J, Kopytko P, Majcher S, Ustianowski P, Dziedziejko V, et al. Effect of FTO and IGF2BP2 gene polymorphisms on duration of pregnancy and Apgar scores in women with gestational diabetes. J Obstet Gynaecol. 2019;39(2):151-6. https://doi.org/10.1080/01443615.2018.1502263 PMid:30371117 DOI: https://doi.org/10.1080/01443615.2018.1502263

Chang YC, Liu PH, Yu YH, Kuo SS, Chang TJ, Jiang YD, et al. Validation of type 2 diabetes risk variants identified by genome-wide association studies in han chinese population: A replication study and meta-analysis. PLoS One. 2014;9(4):e95045. https://doi.org/10.1371/journal.pone.0095045 PMid:24736664 DOI: https://doi.org/10.1371/journal.pone.0095045

Lasram K, Ben Halim N, Benrahma H, Mediene-Benchekor S, Arfa I, Hsouna S, et al. Contribution of CDKAL1 rs7756992 and IGF2BP2 rs4402960 polymorphisms in type 2 diabetes, diabetic complications, obesity risk and hypertension in the Tunisian population. J Diabetes. 2015;7(1):102-13. https://doi.org/10.1111/1753-0407.12147 PMid:24636221 DOI: https://doi.org/10.1111/1753-0407.12147

Al-Sinani S. Association of gene variants with susceptibility to type 2 diabetes among Omanis. World J Diabete. 2015;6(2):358-66. https://doi.org/10.4239/wjd.v6.i2.358 PMid:25789119 DOI: https://doi.org/10.4239/wjd.v6.i2.358

Wu J, Wu J, Zhou Y, Zou H, Guo S, Liu J, et al. Quantitative assessment of the variation in IGF2BP2 gene and type 2 diabetes risk. Acta Diabetol. 2012;49 Suppl 1:S87-97. https://doi.org/10.1007/s00592-011-0336-3 PMid:22015911 DOI: https://doi.org/10.1007/s00592-011-0336-3

American Diabetes Association. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43 Suppl 1:S14-31. https://doi.org/10.2337/dc20-S002 PMid:31862745 DOI: https://doi.org/10.2337/dc20-S002

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9. https://doi.org/10.1007/BF00280883 PMid:3899825 DOI: https://doi.org/10.1007/BF00280883

Lee YH. An overview of meta-analysis for clinicians. Korean J Intern Med. 2018;33(2):277-83. https://doi.org/10.3904/kjim.2016.195 PMid:29277096 DOI: https://doi.org/10.3904/kjim.2016.195

Rao P, Wang H, Fang H, Gao Q, Zhang J, Song M, et al. Association between IGF2BP2 polymorphisms and type 2 diabetes mellitus: A case-control study and meta-analysis. Int J Environ Res Public Health. 2016;13(6):574. https://doi.org/10.3390/ijerph13060574 PMid:27294943 DOI: https://doi.org/10.3390/ijerph13060574

Horikawa Y, Miyake K, Yasuda K, Enya M, Hirota Y, Yamagata K. Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. J Clin Endocrinol Metab. 2008;93(8):3136-41. https://doi.org/10.1210/jc.2008-0452 PMid:18477659 DOI: https://doi.org/10.1210/jc.2008-0452

Tabara Y, Osawa H, Kawamoto R, Onuma H, Shimizu I, Miki T, et al. Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening. Diabetes. 2009;58(2):493-8. https://doi.org/10.2337/db07-1785 PMid:19033397 DOI: https://doi.org/10.2337/db07-1785

Sargazi S, Heidari Nia M, Saravani R, Jafari Shahroudi M, Jahantigh D, Shakiba M. IGF2BP2 polymorphisms as genetic biomarkers for either schizophrenia or type 2 diabetes mellitus: A case-control study. Gene Rep. 2020;20(3):100680. https://doi.org/10.1016/j.genrep.2020.100680 DOI: https://doi.org/10.1016/j.genrep.2020.100680

Ali W. Association of common variants in the IGF2BP2 gene with type 2 diabetes. Sohag Med J. 2021;25(2):62-9. https://doi.org/10.21608/smj.2021.67655.1237 DOI: https://doi.org/10.21608/smj.2021.67655.1237

Wu Y, Li H, Loos R, Yu Z, Ye X, Chen L, et al. Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/ IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes. 2008;57(10):2834-42. https://doi.org/10.2337/db08-0047 PMid:18633108 DOI: https://doi.org/10.2337/db08-0047

Huang Q, Yin JY, Dai XP, Pei Q, Dong M, Zhou ZG, et al. IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population. Acta Pharmacol Sin. 2010;31(6):709-17. https://doi.org/10.1038/aps.2010.47 PMid:20523342 DOI: https://doi.org/10.1038/aps.2010.47

Greenwald W, Chiou J, Yan J, Qiu Y, Dai N, Wang A, et al. Pancreatic islet chromatin accessibility and conformation reveals distal enhancer networks of type 2 diabetes risk. Nat Commun. 2019;10(1):2078. https://doi.org/10.1038/s41467-019-09975-4 PMid:31064983 DOI: https://doi.org/10.1038/s41467-019-09975-4

Huang T, Wang L, Bai M, Zheng J, Yuan D, He Y, et al. Influence of IGF2BP2, HMG20A, and HNF1B genetic polymorphisms on the susceptibility to type 2 diabetes mellitus in Chinese Han population. Biosci Rep. 2020;40(5):BSR20193955. https://doi.org/10.1042/BSR20193955 PMid:32329795 DOI: https://doi.org/10.1042/BSR20193955

Girirajan S, Campbell C, Eichler E. Bivariate Genome- Wide Association Study of Depressive Symptoms with Type 2 Diabetes and Quantitative Glycemic Traits. Physiol Behav. 2011;176(5):139-48. https://doi.org/10.1097/PSY.0000000000000555. DOI: https://doi.org/10.1097/PSY.0000000000000555

Trinh I, Gluscencova OB, Boulianne GL. An in vivo screen for neuronal genes involved in obesity identifies Diacylglycerol kinase as a regulator of insulin secretion. Mol Metab. 2019;19(10):13-23. https://doi.org/10.1016/j.molmet.2018.10.006 PMid:30389349 DOI: https://doi.org/10.1016/j.molmet.2018.10.006

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Published

2022-05-21

How to Cite

1.
Falih Z, Khodair BAW, Mohammed NI, Mohammed TK. Insulin-like Growth Factor-2 Binding Protein-2 Gene Polymorphisms in Iraqi Patients with Type 2 Diabetes Mellitus. Open Access Maced J Med Sci [Internet]. 2022 May 21 [cited 2024 Apr. 24];10(A):1178-83. Available from: https://oamjms.eu/index.php/mjms/article/view/9754