The single nucleotide polymorphisms rs11761556 and rs12706832 of the leptin gene are associated with type 2 diabetes mellitus in the Iraqi population

Authors

  • Karar N. J. Musafer School of Biomedical Engineering and Health science Universiti Technologi Malaysia, Jalan Iman, 81310 Skudai, Johor, Malaysia
  • Fahrul Z. Huyop Faculty of Science, Universiti Technologi Malaysia, Jalan Hikmah, 81310 Skudai, Johor
  • Mufeed J. Ewadh Clinical Biochemistry Department, Faculty of Medicine, University of Babylon, Hilla, Babil 51001
  • Eko Supriyanto School of Biomedical Engineering and Health Science, Universiti Technologi Malaysia, Jalan Iman, 81310 Skudai, Johor
  • Tahreer M. Al-Thuwaini Department of Animal Production, College of Agriculture, Al-Qasim Green University, Al-Qasim, Babil 51001
  • Mohamed Baqur S Al-Shuhaib Department of Animal Production, College of Agriculture, Al-Qasim Green University, Al-Qasim, Babil 51001 http://orcid.org/0000-0002-6458-2068

DOI:

https://doi.org/10.2298/ABS210129005M

Keywords:

LEP gene, polymorphism, T2DM, rs11761556, rs12706832, rs2167270

Abstract

Paper description:

  • Three high-frequency single-nucleotide polymorphism (SNPs), rs11761556, rs12706832, and rs2167270, of leptin (LEP) gene were screened to investigate association with type 2 diabetes mellitus (T2DM) in Iraqi adults.
  • Significant associations between only two SNPs (rs11761556 and rs12706832) variations and T2DM were observed.
  • Individuals with AA genotype in rs11761556 and rs12706832 had higher body mass index waist circumference, fasting blood glucose, hemoglobin A1c, homeostatic model assessment for insulin resistance, insulin, low-density lipoprotein cholesterol, and triglyceride values than individuals with other genotypes.
  • These LEP gene variations correlate with T2DM and may serve as a marker for assessment of T2DM in the study population.

Abstract: This study was conducted to assess the potential association between leptin (LEP) gene polymorphisms and type 2 diabetes mellitus (T2DM) in Iraqi patients. Genomic DNA was extracted from 120 diabetic subjects and 100 controls. Three specific PCR fragments were designed to flank three highly frequent single nucleotide polymorphism (SNP)s within LEP, rs11761556, rs12706832 and rs2167270. The amplified loci were genotyped by PCR-single-strand conformation polymorphism (SSCP) followed by Sanger sequencing for representative genotypes. Logistic regression analysis was performed to detect the association between the targeted genetic variants and T2DM. PCR-SSCP genotyping showed three banding patterns for all three targeted SNPs. Individuals with the AA genotype in both rs11761556 and rs12706832 SNPs showed significantly higher (P<0.05) body mass index (BMI), waist circumference (WC), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), insulin, low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) values than those with other genotypes. Association analysis revealed that individuals with the A allele exhibited a greater risk of T2DM. Data of the present investigation indicated that both rs11761556 and rs12706832 SNPs exerted a noticeable association with T2DM. The study suggests implementing both rs11761556 and rs12706832 SNPs in the early detection of T2DM.

Downloads

Download data is not yet available.

References

Mohammed SM, Hasan AS, Al-Hindy HAAM, Mousa MJ. C-Reactive Protein is Associated with the Severity of Periodontal Disease—An Observational Study Among Acute Myocardial Infarction Patients. Sys Rev Pharm. 2020;11:252-7.

Al-Mmumin A, Al-Hindy HA-AM. Hyperuricemia Has a Deleterious Role in Patients with Acute Coronary Syndrome Presented with Poor Oral Hygiene. Int J Pharm Sci Res. 2020;12(sp1):193.

Coppari R, Bjørbæk C. Leptin revisited: its mechanism of action and potential for treating diabetes.Nat Rev Drug Discov. 2012;11:692-708.

Wang DX, Kaur Y, Alyass A, Meyre D. A Candidate-Gene Approach Identifies Novel Associations Between Common Variants in/Near Syndromic Obesity Genes and BMI in Pediatric and Adult European Populations. Diabetes. 2019;68:724-32.

Qadir MI. Role of green tea flavonoids and other related contents in cancer prevention. Crit Rev Eukaryot Gene Expr. 2017;27.

Zhang F, Chen Y, Heiman M, DiMarchi R. Leptin: structure, function and biology. Vitam Horm. 2005;71:345-72.

Londraville RL, Prokop JW, Duff RJ, Liu Q, Tuttle M. On the molecular evolution of leptin, leptin receptor, and endospanin. Front Endocrinol. 2017;8:58.

Park H-K, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism. 2015;64:24-34.

Joffe BI, Panz VR, Raal FJ. From lipodystrophy syndromes to diabetes mellitus. The Lancet. 2001;357:1379-81.

Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995;269(5223):540-3.

Ramos-Lobo AM, Donato Jr J. The role of leptin in health and disease. Temperature. 2017;4:258-91.

Lyssenko V, Lupi R, Marchetti P, Del Guerra S, Orho-Melander M, Almgren P, Sjögren M, Ling C, Eriksson KF, Mancarella R, Berglund G. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest. 2007;117(8):2155-63.

Al-Shuhaib MBS. D76V, L161R, and C117S are the most pathogenic amino acid substitutions with several dangerous consequences on leptin structure, function, and stability. Egypt J Med Hum Genet. 2019;20(32):1-12.

Musafer KNJ, Zaman Huyop F, J Ewadh M, Supriyanto E, Rava M. A Systematic Mapping Study on the Risk Factors Leading to Type II Diabetes Mellitus. KIJOMS. 2020;6:6.

Al-Shuhaib M. A comprehensive in silico prediction of the most deleterious missense variants in the bovine LEP gene. BioTechnologia. 2019;100:429-39.

Paracchini V, Pedotti P, Taioli E. Genetics of leptin and obesity: a HuGE review. A J Epidemiol. 2005;162:101-14.

Gonzalez-Sanchez JL, Martinez-Larrad MT, Zabena C, Perez-Barba M, Serrano-Rios M. Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin: insulin ratio in the Spanish population. Diabetologia. 2008;51:1993-7.

Alami FM, Ahmadi M, Bazrafshan H, Tabarraei A, Khosravi A, Tabatabaiefar MA, Samaei NM. Association of the TCF7L2 rs12255372 (G/T) variant with type 2 diabetes mellitus in an Iranian population. Genet Mol Biol. 2012;35(2):413-7.

Roszkowska-Gancarz M, Kurylowicz A, Polosak J, Mossakowska M, Franek E, Puzianowska-Kuźnicka M. Functional polymorphisms of the leptin and leptin receptor genes are associated with longevity and with the risk of myocardial infarction and of type 2 diabetes mellitus. Endokrynol Pol. 2014;65:11-6.

Al Busaidi N, Shanmugam P, Manoharan D. Diabetes in the Middle East: government health care policies and strategies that address the growing diabetes prevalence in the Middle East. Curr Diabetes Rep. 2019;19:8.

Almyah MK, Albadran AI. Screening of LEP gene polymorphisms as a risk factor for obesity and type 2 diabetes in Iraqis. Mol Biol Res Commun. 2019;8:156.

Wasim M, Awan FR, Najam SS, Khan AR, Khan HN. Role of leptin deficiency, inefficiency, and leptin receptors in obesity. Biochem Genet. 2016;54:565-72.

Li HM, Zhang TP, Leng RX, Li XP, Wang DG, Li XM, Ye DQ, Pan HF. Association of leptin and leptin receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population. J Cell Mol Med. 2017;21:1732-41.

Wang H, Wang C, Han W, Geng C, Chen D, Wu B, Zhang J, Wang C, Jiang P. Association of leptin and leptin receptor polymorphisms with coronary artery disease in a North Chinese Han population. Rev Soc Bras Med Trop. 2020;53:e20190388.

Association AD. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36:S11-66.

Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.

Hashim HO, Al-Shuhaib MBS. A Novel DNA Extraction Protocol from Frozen Blood of Normal Individuals and Patients Who Received Systemic Chemotherapy 2020. 2020090683 [Preprint]. 2020 [cited 2020 Sep 18]. Available from: https://doi.org/10.20944/preprints202009.0683.v1

Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012;13:134.

Hashim HO, Al-Shuhaib MBS. Exploring the potential and limitations of PCR-RFLP and PCR-SSCP for SNP detection: A review. J Appl Biotechnol Rep. 2019;6:137-44.

Mohammed AK, Al-Thuwaini TM, Al-Shuhaib MBS. Single nucleotide polymorphism rs7908486 of the tcf7l2 gene is highly associated with obesity in the Iraqi population. Arch Biol Scie. 2020:56.

Byun SO, Fang Q, Zhou H, Hickford JGH. An effective method for silver-staining DNA in large numbers of polyacrylamide gels. Anal Biochem. 2009;385:174-5.

Yeh FC, Yang RC. POPGENE version 1.31, Microsoft window-based freeware for population genetic analysis. University of Alberta and Tim Boyle, Centre for International Forestry Research. Ftp Microsoft Com/Softlib/Slfiles/Hpgl Exe. 1999.

Yong Y, He L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005;15:97.

Duan D, Jhang J, Wu S, Teng M, Hsu L, Ko Y. Modification effect of sex and obesity on the correlation of LEP polymorphisms with leptin levels in Taiwanese obese women. Mol Genet Genomic Med. 2020;8:e1113.

Daniels TE, Sadovnikoff AI, Ridout KK, Lesseur C, Marsit CJ, Tyrka AR. Associations of maternal diet and placenta leptin methylation. Mol Cell Endocrinol. 2020;505:110739.

Li L, Wang J, Ping Z, Li Y, Wang C, Shi Y, Zhou W, Zhang L. Interaction analysis of gene variants of TCF7L2 and body mass index and waist circumference on type 2 diabetes. Clin Nutr. 2020;39:192-7.

Dallel M, Sghaier I, Finan RR, Douma Z, Hachani F, Letaifa DB, Mahjoub T, Almawi WY. Circulating leptin concentration, LEP gene variants and haplotypes, and polycystic ovary syndrome in Bahraini and Tunisian Arab women. Gene. 2019;694:19-25.

Labayen I, Ruiz JR, Moreno LA, Ortega FB, Beghin L, DeHenauw S, Benito PJ, Diaz LE, Ferrari M, Moschonis G, Kafatos A. The effect of ponderal index at birth on the relationships between common LEP and LEPR polymorphisms and adiposity in adolescents. Obesity. 2011;19:2038-45.

Lombard Z, Crowther NJ, Van der Merwe L, Pitamber P, Norris SA, Ramsay M. Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study. BMJ Open. 2012;2.

Nurmi EL, Spilman SL, Whelan F, Scahill LL, Aman MG, McDougle CJ, Arnold LE, Handen B, Johnson C, Sukhodolsky DG, Posey DJ. Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies. Transl Psychiat. 2013;3:e274-e274.

Ovsyannikova IG, White SJ, Larrabee BR, Grill DE, Jacobson RM, Poland GA. Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals. Vaccine. 2014;32:881-7.

Kasim NB, Huri HZ, Vethakkan SR, Ibrahim L, Abdullah BM. Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus. Biomark Med. 2016;10:403-15.

Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014;42:D980-5.

Han HR, Ryu HJ, Cha HS, Go MJ, Ahn Y, Koo BK, Cho YM, Lee HK, Cho NH, Shin C, Shin HD. Genetic variations in the leptin and leptin receptor genes are associated with type 2 diabetes mellitus and metabolic traits in the Korean female population. Clin Genet. 2008;74:105-15.

Nesrine Z, Haithem H, Imen B, Fadoua N, Asma O, Fadhel NM, Ali B. Leptin and Leptin receptor polymorphisms, plasma Leptin levels and obesity in Tunisian volunteers. Int J Clin Exp Pathol. 2018;99:121-30.

Nyante SJ, Gammon MD, Kaufman JS, Bensen JT, Lin DY, Barnholtz-Sloan JS, Hu Y, He Q, Luo J, Millikan RC. Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes. Breast Cancer Res Tr. 2011;129:593-606.

Ma D, Feitosa MF, Wilk JB, Laramie JM, Yu K, Leiendecker-Foster C, Myers RH, Province MA, Borecki IB. Leptin is associated with blood pressure and hypertension in women from the National Heart, Lung, and Blood Institute Family Heart Study. Hypertension. 2009;53:473-9.

Downloads

Published

2021-03-19

How to Cite

1.
Musafer KNJ, Huyop FZ, Ewadh MJ, Supriyanto E, Al-Thuwaini TM, Al-Shuhaib MBS. The single nucleotide polymorphisms rs11761556 and rs12706832 of the leptin gene are associated with type 2 diabetes mellitus in the Iraqi population. Arch Biol Sci [Internet]. 2021Mar.19 [cited 2024Nov.22];73(1):93-101. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/6202

Issue

Vol. 73 No. 1 (2021)

Section

Articles

License

Copyright (c) 2021 Archives of Biological Sciences

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.