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Published in: International Journal of Diabetes in Developing Countries 2/2020

01-04-2020 | Insulins | Original Article

Genetic polymorphism of eNOS (G894T) gene in insulin resistance in type 2 diabetes patients of Pakistani population

Authors: Abdullah Abdo Albegali, Muhammad Shahzad, Saqib Mahmood, Muhammad Ikram Ullah, Ali Amar, Osheen Sajjad

Published in: International Journal of Diabetes in Developing Countries | Issue 2/2020

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Abstract

Background

Insulin resistance associated with type 2 diabetes (T2DM) consequences in the development of metabolc syndrome. Due to the complex mechanism, various pathogenic factors like enviromental and genetic predispositon contribute to the disease pathogenicity. The reduced availability of eNOS has been determined as a mark of insulin resistance pathogenesis.

Objective

The objctive of this study was to investigate genetic polymorphism of eNOS (rs1799983; G894T) with susceptibility of insulin resistance in type 2 diabetes (T2DM) patients from Pakistani population.

Methods

Total of 322 (161 T2DM cases and 161 healthy controls) subjects were recruited for this study. Genomic DNA extraction was carried out by standard phenol-chloroform protocols. PCR amplification of the unique oligonucleotides of eNOS gene was done and restriction fragment analysis (RFLP) was performed by site-specific enzyme BanII.

Results

The frequency of GG (wild genotype) was higher (77.6%) in cases than in controls (47.2%), heterozygous GT genotype higher in controls than patients (OR = 0.26, p < 0.0005 and after adjustment, OR = 0.34, p = 0.091). Different genetic models like dominant model of GT&TT was higher in controls than patients (OR 0.26, p < 0.0005; OR 0.29, p = 0.038 respectively) and log-additive model indicated the significant protective effect of the genotype before and after adjustment for the confounding factors.

Conclusion

This study demonstrates that there is no association between eNOS rs1799983 polymorphism and insulin resistance in T2DM patients of Pakistani population.
Literature
3.
go back to reference Bae J, Kim IJ, Hong SH, Sung JH, Lim SW, Cha DH. Association of endothelial nitric oxide synthase polymorphisms with coronary artery disease in Korean individuals with or without diabetes mellitus. Exp Ther Med. 2010;1:719–24.CrossRefPubMedPubMedCentral Bae J, Kim IJ, Hong SH, Sung JH, Lim SW, Cha DH. Association of endothelial nitric oxide synthase polymorphisms with coronary artery disease in Korean individuals with or without diabetes mellitus. Exp Ther Med. 2010;1:719–24.CrossRefPubMedPubMedCentral
4.
go back to reference Chandrasekaran S, Sivani S, Sudarsanam D. Evaluation of single nucleotide polymorphism C825T in the GNB3 gene with the development of type 2 diabetes of the South Indian population. Int J Pharm Sci Res. 2012;13(1):249–57. Chandrasekaran S, Sivani S, Sudarsanam D. Evaluation of single nucleotide polymorphism C825T in the GNB3 gene with the development of type 2 diabetes of the South Indian population. Int J Pharm Sci Res. 2012;13(1):249–57.
6.
go back to reference Guzik TJ, Black E, West NE, McDonald D, Ratnatunga C, Pillai R. Relationship between the G894T polymorphism (Glu298Asp variant) in endothelial nitric oxide synthase and nitric oxide-mediated endothelial function in human atherosclerosis. Am J Med Genet. 2001;100(2):130–7.CrossRefPubMed Guzik TJ, Black E, West NE, McDonald D, Ratnatunga C, Pillai R. Relationship between the G894T polymorphism (Glu298Asp variant) in endothelial nitric oxide synthase and nitric oxide-mediated endothelial function in human atherosclerosis. Am J Med Genet. 2001;100(2):130–7.CrossRefPubMed
9.
go back to reference Guo X, Cheng S, Taylor KD, Cui J, Hughes R, Quiñones MJ. Hypertension genes are genetic markers for insulin sensitivity and resistance. Hypertension. 2005;45(4):799–803.CrossRefPubMed Guo X, Cheng S, Taylor KD, Cui J, Hughes R, Quiñones MJ. Hypertension genes are genetic markers for insulin sensitivity and resistance. Hypertension. 2005;45(4):799–803.CrossRefPubMed
10.
go back to reference Demova H, Daniela JB, Hannes R, Bohumir K, Ludmila P, Ivan B. Gene polymorphisms in patients with type 2 diabetes and diabetic nephropathy. Cent Eur J Biol. 2012;7(2):210–8. Demova H, Daniela JB, Hannes R, Bohumir K, Ludmila P, Ivan B. Gene polymorphisms in patients with type 2 diabetes and diabetic nephropathy. Cent Eur J Biol. 2012;7(2):210–8.
11.
go back to reference Conen D, Glynn RJ, Buring JE, Ridker PM, Zee RY, et al. Reninangiotensin and endothelial nitric oxide synthase gene polymorphisms are not associated with the risk of incident type 2 diabetes mellitus: a prospective cohort study. J Intern Med. 2008;263(4):376–85.CrossRefPubMed Conen D, Glynn RJ, Buring JE, Ridker PM, Zee RY, et al. Reninangiotensin and endothelial nitric oxide synthase gene polymorphisms are not associated with the risk of incident type 2 diabetes mellitus: a prospective cohort study. J Intern Med. 2008;263(4):376–85.CrossRefPubMed
12.
go back to reference Dlugos AM, Hamidovic A, Palmer AA, de Wit H. Further evidence of association between amphetamine response and SLC6A2 gene variants. Psychopharmacology. 2009;206:501–11.CrossRefPubMedPubMedCentral Dlugos AM, Hamidovic A, Palmer AA, de Wit H. Further evidence of association between amphetamine response and SLC6A2 gene variants. Psychopharmacology. 2009;206:501–11.CrossRefPubMedPubMedCentral
13.
go back to reference Dellamea BS, Pinto LCF, Leitão CB, Santos KG, Canani LHS. Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review and metaanalysis. BMC Med Genet. 2014;15:9.CrossRefPubMedPubMedCentral Dellamea BS, Pinto LCF, Leitão CB, Santos KG, Canani LHS. Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review and metaanalysis. BMC Med Genet. 2014;15:9.CrossRefPubMedPubMedCentral
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
16.
go back to reference Erdogan M, Kulaksizoglu M, Tetik A, Solmaz S, Kucukaslan AS, Eroglu Z. The relationship of the endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) gene polymorphism in Turkish type 2 diabetic patients with and without diabetic foot ulcers. Foot (Edinb). 2018;37:5–10. https://doi.org/10.1016/j.foot.2018.06.006.CrossRef Erdogan M, Kulaksizoglu M, Tetik A, Solmaz S, Kucukaslan AS, Eroglu Z. The relationship of the endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) gene polymorphism in Turkish type 2 diabetic patients with and without diabetic foot ulcers. Foot (Edinb). 2018;37:5–10. https://​doi.​org/​10.​1016/​j.​foot.​2018.​06.​006.CrossRef
22.
go back to reference Ansarimoghaddam A, Adineh HA, Zareban I, Iranpour S, HosseinZadeh A, Kh F. Prevalence of metabolic syndrome in Middle-East countries: Meta-analysis of cross-sectional studies. Diabetes Metab Syndr. 2018;12(2):195–201.CrossRefPubMed Ansarimoghaddam A, Adineh HA, Zareban I, Iranpour S, HosseinZadeh A, Kh F. Prevalence of metabolic syndrome in Middle-East countries: Meta-analysis of cross-sectional studies. Diabetes Metab Syndr. 2018;12(2):195–201.CrossRefPubMed
25.
go back to reference Yoshimura T, Hisatomi A, Kajihara S, Yasutake T, Ogawa Y, Mizuta T, et al. The relationship between insulin resistance and polymorphisms of the endothelial nitric oxide synthase gene in patients with coronary artery disease. J Atheroscler Thromb. 2003;10(1):43–7.CrossRefPubMed Yoshimura T, Hisatomi A, Kajihara S, Yasutake T, Ogawa Y, Mizuta T, et al. The relationship between insulin resistance and polymorphisms of the endothelial nitric oxide synthase gene in patients with coronary artery disease. J Atheroscler Thromb. 2003;10(1):43–7.CrossRefPubMed
26.
go back to reference Santos KG, Crispim D, Canani LH, Ferrugem PT, Gross JL, Roisenberg I. Relationship of endothelial nitric oxide synthase (eNOS) gene polymorphisms with diabetic retinopathy in Caucasians with type 2 diabetes. Ophthalmic Genet. 2012;33(1):23–7.CrossRefPubMed Santos KG, Crispim D, Canani LH, Ferrugem PT, Gross JL, Roisenberg I. Relationship of endothelial nitric oxide synthase (eNOS) gene polymorphisms with diabetic retinopathy in Caucasians with type 2 diabetes. Ophthalmic Genet. 2012;33(1):23–7.CrossRefPubMed
27.
go back to reference Shah VN, Cheema BS, Kohli HS, Sharma R, Khullar M, et al. Endothelial nitric oxide synthase gene polymorphism and the risk of diabetic neuropathy in Asian Indian patients with type 2 diabetes. J Diabetes Metab. 2013;4:243.CrossRef Shah VN, Cheema BS, Kohli HS, Sharma R, Khullar M, et al. Endothelial nitric oxide synthase gene polymorphism and the risk of diabetic neuropathy in Asian Indian patients with type 2 diabetes. J Diabetes Metab. 2013;4:243.CrossRef
28.
go back to reference Srivastava K, Biswas UK, Narang R, Varghese JJ, Das N. Prevalence of eNOS Glu298Asp polymorphism in healthy volunteers from a region of northern India. Community Genet. 2005;8:180–3.PubMed Srivastava K, Biswas UK, Narang R, Varghese JJ, Das N. Prevalence of eNOS Glu298Asp polymorphism in healthy volunteers from a region of northern India. Community Genet. 2005;8:180–3.PubMed
29.
go back to reference Garme Y, Moudi M, Saravani R, Galavi H. Nitric oxide synthase 2 polymorphisms (rs2779248T/C and rs1137933C/T) and the risk of type 2 diabetes in Zahedan, Southeastern Iran. Iran J Public Health. 2018;47(11):1734–41.PubMedPubMedCentral Garme Y, Moudi M, Saravani R, Galavi H. Nitric oxide synthase 2 polymorphisms (rs2779248T/C and rs1137933C/T) and the risk of type 2 diabetes in Zahedan, Southeastern Iran. Iran J Public Health. 2018;47(11):1734–41.PubMedPubMedCentral
30.
go back to reference de Syllos RW, Sandrim VC, Lisboa HR, Tres GS, Tanus-Santos JE. Endothelial nitric oxide synthase genotype and haplotype are not associated with diabetic retinopathy in diabetes type 2 patients. Nitric Oxide. 2006;15(4):417–22.CrossRefPubMed de Syllos RW, Sandrim VC, Lisboa HR, Tres GS, Tanus-Santos JE. Endothelial nitric oxide synthase genotype and haplotype are not associated with diabetic retinopathy in diabetes type 2 patients. Nitric Oxide. 2006;15(4):417–22.CrossRefPubMed
31.
go back to reference Monti LD, Barlassina C, Citterio L, Galluccio E, Berzuini C, Setola E, et al. Endothelial nitric oxide synthase polymorphisms are associated with type 2 diabetes and the insulin resistance syndrome. Diabetes. 2003;52(5):1270–5.CrossRefPubMed Monti LD, Barlassina C, Citterio L, Galluccio E, Berzuini C, Setola E, et al. Endothelial nitric oxide synthase polymorphisms are associated with type 2 diabetes and the insulin resistance syndrome. Diabetes. 2003;52(5):1270–5.CrossRefPubMed
32.
go back to reference Rittig K, Holder K, Stock J, Tschritter O, Peter A, Stefan N, et al. Endothelial NO-synthase intron 4 polymorphism is associated with disturbed in vivo nitric oxide production in individuals prone to type 2 diabetes. Horm Metab Res. 2008;40(1):13–7.CrossRefPubMed Rittig K, Holder K, Stock J, Tschritter O, Peter A, Stefan N, et al. Endothelial NO-synthase intron 4 polymorphism is associated with disturbed in vivo nitric oxide production in individuals prone to type 2 diabetes. Horm Metab Res. 2008;40(1):13–7.CrossRefPubMed
Metadata
Title
Genetic polymorphism of eNOS (G894T) gene in insulin resistance in type 2 diabetes patients of Pakistani population
Authors
Abdullah Abdo Albegali
Muhammad Shahzad
Saqib Mahmood
Muhammad Ikram Ullah
Ali Amar
Osheen Sajjad
Publication date
01-04-2020
Publisher
Springer India
Published in
International Journal of Diabetes in Developing Countries / Issue 2/2020
Print ISSN: 0973-3930
Electronic ISSN: 1998-3832
DOI
https://doi.org/10.1007/s13410-019-00775-6

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