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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

The Influence of TNF-α, IL-6, TGF-β1, IFN-γ, IL-10 Polymorphisms on Predisposition to Diabetes Mellitus among Jordanian Patients

Author(s): Sawsan I. Khdair*, Ola S. Al-Naimat, Wassan Jarrar, Walid Al-Qerem and Feras A. Khudeir

Volume 23, Issue 5, 2023

Published on: 18 November, 2022

Page: [681 - 691] Pages: 11

DOI: 10.2174/1871530322666220827143530

Price: $65

Abstract

Background: Diabetes mellitus is a long-term disorder with high prevalence globally. It can be classified into two types: Type 1 diabetes and Type 2 diabetes mellitus. Diabetes mellitus is considered a multifactorial disorder in which genetic factors such as cytokines play a major role. Cytokines play a role in immune modulation and are associated with the development of diabetes mellitus. Single nucleotide polymorphisms in cytokines were studied extensively in different populations to determine their association with a predisposition to diabetes mellitus.

Objective: The aim of this study was to estimate the frequency of single nucleotide polymorphisms in the cytokine genes TNF-α, TGF-β, IL-6, IL-10, and IFN-γ in 102 Jordanian diabetes mellitus patients in comparison to 50 controls and their association to diabetes mellitus susceptibility.

Methods: Analysis was performed using the highly specific polymerase chain reaction-sequence specific primers methodology.

Results: Our findings showed that the IL-10-1082 G/G genotype (P = 0.02) and the TGF-β1 codon 25*G allele (P < 0.01) may be considered risk factors for type 2 diabetes mellitus. In addition, the IFN-γ-874*A allele (P = 0.04) seems to increase the predisposition to type 1 diabetes.

Conclusion: Our study showed that the IL-10-1082 G/G genotype and TGF-β1 codon 25*G allele are associated with type 2 diabetes mellitus while the IFN- γ -874*A allele is associated with type 1 diabetes. Our findings may help in the early detection of diabetes mellitus, which would in turn help in undergoing the needed preventative measures to delay the onset of diabetes mellitus.

Keywords: Cytokines, SNPs, Jordan, type 1 diabetes, type 2 diabetes mellitus, polymorphisms.

Graphical Abstract
[1]
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2010, 33(Suppl. 1), S62-S69.
[http://dx.doi.org/10.2337/dc10-S062] [PMID: 20042775]
[2]
Yaochite, J.N.U.; Carlos, D. Th17 cell-mediated responses in type 1 diabetes pathogenesis. J. Clin. Cell. Immunol.,, 2012, S10, 06.
[http://dx.doi.org/10.4172/2155-9899.S10-006]
[3]
Kosiborod, M.; Gomes, M.B.; Nicolucci, A.; Pocock, S.; Rathmann, W.; Shestakova, M.V.; Watada, H.; Shimomura, I.; Chen, H.; Cid-Ruzafa, J.; Fenici, P.; Hammar, N.; Surmont, F.; Tang, F.; Khunti, K. Vascular complications in patients with type 2 diabetes: Prevalence and associated factors in 38 countries (the DISCOVER study program). Cardiovasc. Diabetol., 2018, 17(1), 150.
[http://dx.doi.org/10.1186/s12933-018-0787-8] [PMID: 30486889]
[4]
International Diabetes Federation. IDF Diabetes Atlas. https://www.who.int/news-room/fact-sheets/detail/diabetes
[5]
International Diabetes Federation. IDF Diabetes Atlas, 2019.
[6]
Saeedi, P.; Petersohn, I.; Salpea, P.; Malanda, B.; Karuranga, S.; Unwin, N.; Colagiuri, S.; Guariguata, L.; Motala, A.A.; Ogurtsova, K. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th Edition. Diabetes Res. Clin. Pract.,, 2019, 157, 10783.
[http://dx.doi.org/10.1016/j.diabres.2019.107843]
[7]
Patterson, C.C.; Karuranga, S.; Salpea, P.; Saeedi, P.; Dahlquist, G.; Soltesz, G.; Ogle, G.D. Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas, 9th Edition. Diabetes Res. Clin. Pract.,, 2019, 157, 107842.
[http://dx.doi.org/10.1016/j.diabres.2019.107842]
[8]
Fatima, N.; Faisal, S.M.; Zubair, S.; Ajmal, M.; Siddiqui, S.S.; Moin, S.; Owais, M. Role of pro-inflammatory cytokines and biochemical markers in the pathogenesis of type 1 diabetes: Correlation with age and glycemic condition in diabetic human subjects. PLoS One, 2016, 11(8), e0161548.
[http://dx.doi.org/10.1371/journal.pone.0161548] [PMID: 27575603]
[9]
Wang, Z.; Xie, Z.; Lu, Q.; Chang, C.; Zhou, Z. Beyond genetics: What causes type 1 diabetes. Clin. Rev. Allergy Immunol., 2017, 52(2), 273-286.
[http://dx.doi.org/10.1007/s12016-016-8592-1] [PMID: 27878451]
[10]
Hu, F.B. Globalization of diabetes. Diabetes Care, 2011, 34(6), 1249-1257.
[http://dx.doi.org/10.2337/dc11-0442] [PMID: 21617109]
[11]
Murea, M.; Ma, L.; Freedman, B.I. Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications. Rev. Diabet. Stud., 2012, 9(1), 6-22.
[http://dx.doi.org/10.1900/RDS.2012.9.6] [PMID: 22972441]
[12]
Jarab, A.S.; Alefishat, E.; Mukattash, T.L.; Albawab, A.Q.; Abu-Farha, R.K.; McElnay, J.C. Exploring variables associated with poor health-related quality of life in patients with type 2 diabetes in Jordan. J. Pharm. Health Serv. Res., 2019, 10(2), 211-217.
[http://dx.doi.org/10.1111/jphs.12255]
[13]
Ad’hiah, A.H.; Al-rikabi, A.H.; Ahmed, Z.A.; Kamil, L.A. HLA-A, -B, -DRB1 and -DQB1 polymorphisms among Iraqi Arabs. Hum. Immunol., 2020, 81(5), 191-192.
[http://dx.doi.org/10.1016/j.humimm.2020.03.006] [PMID: 32223986]
[14]
Hamzeh, A.R.; Nair, P.; Al Ali, M.T. The profile of HLA-DRB1 alleles in Arabs with type 1 diabetes; meta-analyses. HLA, 2016, 87(1), 25-30.
[http://dx.doi.org/10.1111/tan.12717] [PMID: 26818122]
[15]
Erlich, H.; Valdes, A.M.; Noble, J.; Carlson, J.A.; Varney, M.; Concannon, P.; Mychaleckyj, J.C.; Todd, J.A.; Bonella, P.; Fear, A.L.; Lavant, E.; Louey, A.; Moonsamy, P. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: Analysis of the type 1 diabetes genetics consortium families. Diabetes, 2008, 57(4), 1084-1092.
[http://dx.doi.org/10.2337/db07-1331] [PMID: 18252895]
[16]
Sirdah, M.M.; Reading, N.S. Genetic predisposition in type 2 diabetes: A promising approach towards a personalized management of diabetes. Clin. Genet., 2020, 98(6), 525-547.
[http://dx.doi.org/10.1111/cge.13772]
[17]
Xue, A.; Wu, Y.; Zhu, Z.; Zhang, F.; Kemper, K.E.; Zheng, Z.; Yengo, L.; Lloyd-Jones, L.R.; Sidorenko, J.; Wu, Y.; McRae, A.F.; Visscher, P.M.; Zeng, J.; Yang, J. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat. Commun., 2018, 9(1), 2941.
[http://dx.doi.org/10.1038/s41467-018-04951-w] [PMID: 30054458]
[18]
Asamoah, E.A.; Obirikorang, C.; Acheampong, E.; Annani-Akollor, M.E.; Laing, E.F.; Owiredu, E.W.; Anto, E.O. Heritability and genetics of type 2 diabetes mellitus in Sub-Saharan Africa: A systematic review and meta-analysis. J. Diabetes Res., 2020, 2020, 1-11.
[http://dx.doi.org/10.1155/2020/3198671] [PMID: 32685554]
[19]
Grunnet, L.G.; Mandrup-Poulsen, T. Cytokines and type 1 diabetes: A numbers game. Diabetes, 2011, 60(3), 697-699.
[http://dx.doi.org/10.2337/db10-1782] [PMID: 21357470]
[20]
Akash, M.S.H.; Rehman, K.; Liaqat, A. Tumor necrosis factor-alpha: Role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J. Cell. Biochem., 2018, 119(1), 105-110.
[http://dx.doi.org/10.1002/jcb.26174] [PMID: 28569437]
[21]
Rehman, K.; Akash, M.S.H.; Liaqat, A.; Kamal, S.; Qadir, M.I.; Rasul, A. Role of interleukin-6 in development of insulin resistance and type 2 diabetes mellitus. Crit. Rev. Eukaryot. Gene Expr., 2017, 27(3), 229-236.
[http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2017019712] [PMID: 29199608]
[22]
Dinarello, C.A. Historical insights into cytokines. Eur. J. Immunol., 2007, 37(Suppl. 1), S34-S45.
[http://dx.doi.org/10.1002/eji.200737772] [PMID: 17972343]
[23]
Ferreira, L. Cytokines and interferons: Types and functions. In: Autoantibodies and Cytokines; Khan, W.A., Ed.; IntechOpen: London, UK, 2019.
[http://dx.doi.org/10.5772/intechopen.74550]
[24]
Saxena, M.; Agrawal, C.G.; Bid, H.K.; Banerjee, M. An interleukin-10 gene promoter polymorphism (-592A/C) associated with type 2 diabetes: A North Indian study. Biochem. Genet., 2012, 50(7-8), 549-559.
[http://dx.doi.org/10.1007/s10528-012-9499-z] [PMID: 22298356]
[25]
Erbilgin, A.; Civelek, M.; Romanoski, C.E.; Pan, C.; Hagopian, R.; Berliner, J.A.; Lusis, A.J. Identification of CAD candidate genes in GWAS loci and their expression in vascular cells. J. Lipid Res., 2013, 54(7), 1894-1905.
[http://dx.doi.org/10.1194/jlr.M037085] [PMID: 23667179]
[26]
Shiba, T.; Higashi, N.; Nishimura, Y. Hyperglycaemia due to insulin resistance caused by interferon-γ. Diabet. Med., 1998, 15(5), 435-436.
[http://dx.doi.org/10.1002/(SICI)1096-9136(199805)15:5<435:AID-DIA566>3.0.CO;2-N] [PMID: 9609368]
[27]
Banerjee, M.; Saxena, M. Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus. World J. Diabetes, 2014, 5(4), 493-504.
[http://dx.doi.org/10.4239/wjd.v5.i4.493] [PMID: 25126395]
[28]
Ichinose, K.; Kawasaki, E.; Eguchi, K. Recent advancement of understanding pathogenesis of type 1 diabetes and potential relevance to diabetic nephropathy. Am. J. Nephrol., 2007, 27(6), 554-564.
[http://dx.doi.org/10.1159/000107758] [PMID: 17823503]
[29]
Hollegaard, M.V.; Bidwell, J.L. Cytokine gene polymorphism in human disease: On-line databases, Supplement 3. Genes Immun., 2006, 7(4), 269-276.
[http://dx.doi.org/10.1038/sj.gene.6364301] [PMID: 16642032]
[30]
Diana, M. Effect of cytokine and pharmacogenomic genetic. Curr. Opin. Immunol., 2008, 20(5), 614-625.
[http://dx.doi.org/10.1016/j.coi.2008.08.002]
[31]
Smith, A.J.P.; Humphries, S.E. Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine Growth Factor Rev., 2009, 20(1), 43-59.
[http://dx.doi.org/10.1016/j.cytogfr.2008.11.006] [PMID: 19038572]
[32]
Ashif, C.M.; Balasubramanian, T. A review on role of cytokine gene polymorphisms in type 2 diabetes mellitus. Int. J. Pharm. Sci. Rev. Res., 2016, 39, 85-92.
[33]
Saxena, M.; Srivastava, N.; Banerjee, M. Association of IL-6, TNF-α and IL-10 gene polymorphisms with type 2 diabetes mellitus. Mol. Biol. Rep., 2013, 40(11), 6271-6279.
[http://dx.doi.org/10.1007/s11033-013-2739-4] [PMID: 24057184]
[34]
Aminkeng, F.; Van Autreve, J.E.; Koeleman, B.P.C.; Quartier, E.; Van Schravendijk, C.; Gorus, F.K.; Van der Auwera, B.J.R. TNFa microsatellite polymorphism modulates the risk of type 1 diabetes in the Belgian population, independent of HLA-DQ. Hum. Immunol., 2007, 68(8), 690-697.
[http://dx.doi.org/10.1016/j.humimm.2007.05.001] [PMID: 17678725]
[35]
Javor, J.; Ferencik, S.; Bucova, M.; Stuchlikova, M.; Martinka, E.; Barak, L.; Strbova, L.; Grosse-Wilde, H.; Buc, M. Polymorphisms in the genes encoding TGF-beta1, TNF-α and IL-6 show association with type 1 diabetes mellitus in the Slovak population. Arch. Immunol. Ther. Exp. (Warsz.), 2010, 58(5), 385-393.
[http://dx.doi.org/10.1007/s00005-010-0092-z] [PMID: 20686866]
[36]
Awad, S.F.; Huangfu, P.; Dargham, S.R.; Ajlouni, K.; Batieha, A.; Khader, Y.S.; Critchley, J.A.; Abu-Raddad, L.J. Characterizing the type 2 diabetes mellitus epidemic in Jordan up to 2050. Sci. Rep., 2020, 10(1), 21001.
[http://dx.doi.org/10.1038/s41598-020-77970-7] [PMID: 33273500]
[37]
Al-Qerem, W.; Al Bawab, A.Q.; Hammad, A.; Ling, J.; Alasmari, F.; Alasmari, F. Willingness of the Jordanian population to receive a COVID-19 booster dose: A cross-sectional study. Vaccines (Basel), 2022, 10(3), 410.
[http://dx.doi.org/10.3390/vaccines10030410] [PMID: 35335042]
[38]
Eskdale, J.; Gallagher, G.; Verweij, C.L.; Keijsers, V.; Westendorp, R.G.J.; Huizinga, T.W.J. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc. Natl. Acad. Sci. USA, 1998, 95(16), 9465-9470.
[http://dx.doi.org/10.1073/pnas.95.16.9465] [PMID: 9689103]
[39]
Westendorp, R.G.J.; Langermans, J.A.M.; Huizinga, T.W.J.; Elouali, A.H.; Verweij, C.L.; Boomsma, D.I.; Vandenbrouke, J.P. Genetic influence on cytokine production and fatal meningococcal disease. Lancet, 1997, 349(9046), 170-173.
[http://dx.doi.org/10.1016/S0140-6736(96)06413-6] [PMID: 9111542]
[40]
Turner, D.M.; Williams, D.M.; Sankaran, D.; Lazarus, M.; Sinnott, P.J.; Hutchinson, I.V. An investigation of polymorphism in the interleukin-10 gene promoter. Eur. J. Immunogenet., 1997, 24(1), 1-8.
[http://dx.doi.org/10.1111/j.1365-2370.1997.tb00001.x] [PMID: 9043871]
[41]
Li, M.O.; Wan, Y.Y.; Sanjabi, S.; Robertson, A.K.L.; Flavell, R.A. Transforming growth factor-β regulation of immune responses. Annu. Rev. Immunol., 2006, 24, 99-146.
[http://dx.doi.org/10.1146/annurev.immunol.24.021605.090737]
[42]
Awad, M.R.; El-Gamel, A.; Hasleton, P.; Turner, D.M.; Sinnott, P.J.; Hutchinson, I.V. Genotypic variation in the transforming growth factor-beta1 gene: Association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation, 1998, 66(8), 1014-1020.
[http://dx.doi.org/10.1097/00007890-199810270-00009] [PMID: 9808485]
[43]
Herder, C.; Zierer, A.; Koenig, W.; Roden, M.; Meisinger, C.; Thorand, B. Transforming growth factor-beta1 and incident type 2 diabetes: Results from the MONICA/KORA case-cohort study, 1984-2002. Diabetes Care, 2009, 32(10), 1921-1923.
[http://dx.doi.org/10.2337/dc09-0476] [PMID: 19592635]
[44]
Miljkovic, D.; Cvetkovic, I.; Momcilovic, M.; Maksimovic-Ivanic, D.; Stosic-Grujicic, S.; Trajkovic, V. Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells. Cell. Mol. Life Sci., 2005, 62(22), 2658-2668.
[http://dx.doi.org/10.1007/s00018-005-5259-0] [PMID: 16261264]
[45]
Beránek, M.; Kan̆ková, K.; Benes̆, P.; Izakovic̆ová-Hollá, L.; Znojil, V.; Hájek, D.; Vlková, E.; Vácha, J. Polymorphism R25P in the gene encoding transforming growth factor-beta (TGF-β1) is a newly identified risk factor for proliferative diabetic retinopathy. Am. J. Med. Genet., 2002, 109(4), 278-283.
[http://dx.doi.org/10.1002/ajmg.10372] [PMID: 11992481]
[46]
El-Sherbini, S.M.; Shahen, S.M.; Mosaad, Y.M.; Abdelgawad, M.S.; Talaat, R.M. Gene polymorphism of transforming growth factor-β1 in Egyptian patients with type 2 diabetes and diabetic nephropathy. Acta Biochim. Biophys. Sin. (Shanghai), 2013, 45(4), 330-338.
[http://dx.doi.org/10.1093/abbs/gmt003] [PMID: 23399816]
[47]
Tsiavou, A.; Hatziagelaki, E.; Chaidaroglou, A.; Manginas, A.; Koniavitou, K.; Degiannis, D.; Raptis, S.A. TNF-α TGF-beta1, IL-10, IL-6, gene polymorphisms in Latent Autoimmune Diabetes of Adults (LADA) and type 2 diabetes mellitus. J. Clin. Immunol., 2004, 24(6), 591-599.
[http://dx.doi.org/10.1007/s10875-004-6239-0] [PMID: 15622443]
[48]
Lalani, I.; Bhol, K.; Ahmed, A.R. Interleukin-10: Biology, role in inflammation and autoimmunity. Ann. Allergy Asthma Immunol., 1997, 79(6), 469-484.
[http://dx.doi.org/10.1016/S1081-1206(10)63052-9] [PMID: 9433360]
[49]
Helaly, M.A.H.; Hatata, E.S.Z.; Abu-Elmagd, M.; Ibrahem, E.F.; Alsaid, A.; Abd El-Aal, I.A.; Settin, A. Association of IL-10 and IL-6 gene polymorphisms with type 2 diabetes mellitus among Egyptian patients. Electron. J. Gen. Med., 2013, 10(3), 158-162.
[http://dx.doi.org/10.29333/ejgm/82250]
[50]
Kolla, V.K.; Madhavi, G.; Pulla Reddy, B.; Srikanth Babu, B.M.V.; Yashovanthi, J.; Valluri, V.L.; Ramesh, J.; Akka, J. Association of tumor necrosis factor alpha, interferon gamma and interleukin 10 gene polymorphisms with peripheral neuropathy in South Indian patients with type 2 diabetes. Cytokine, 2009, 47(3), 173-177.
[http://dx.doi.org/10.1016/j.cyto.2009.06.007] [PMID: 19608431]
[51]
Bai, H.; Jing, D.; Guo, A.; Yin, S. Association between interleukin 10 gene polymorphisms and risk of type 2 diabetes mellitus in a Chinese population. J. Int. Med. Res., 2014, 42(3), 702-710.
[http://dx.doi.org/10.1177/0300060513505813] [PMID: 24758873]
[52]
Ayelign, B.; Negash, M.; Andualem, H.; Wondemagegn, T.; Kassa, E.; Shibabaw, T.; Akalu, Y.; Molla, M.D. Association of IL-10 - 1082 A/G) and IL-6 (- 174 G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population. BMC Endocr. Disord., 2021, 21(1), 70.
[http://dx.doi.org/10.1186/s12902-021-00738-1] [PMID: 33858419]
[53]
Suárez, A.; Castro, P.; Alonso, R.; Mozo, L.; Gutiérrez, C. Interindividual variations in constitutive interleukin-10 messenger RNA and protein levels and their association with genetic polymorphisms1. Transplantation, 2003, 75(5), 711-717.
[http://dx.doi.org/10.1097/01.TP.0000055216.19866.9A] [PMID: 12640314]
[54]
Azar, S.T.; Tamim, H.; Beyhum, H.N.; Habbal, M.Z.; Almawi, W.Y.; Type, I. Type I (insulin-dependent) diabetes is a Th1- and Th2-mediated autoimmune disease. Clin. Diagn. Lab. Immunol., 1999, 6(3), 306-310.
[http://dx.doi.org/10.1128/CDLI.6.3.306-310.1999] [PMID: 10225827]
[55]
Pravica, V.; Perrey, C.; Stevens, A.; Lee, J.H.; Hutchinson, I.V. A single nucleotide polymorphism in the first intron of the human IFN-γ gene. Hum. Immunol., 2000, 61(9), 863-866.
[http://dx.doi.org/10.1016/S0198-8859(00)00167-1] [PMID: 11053629]
[56]
Khdair, S.I.; Jarrar, W.; Jarrar, Y.B.; Bataineh, S.; Al-Khaldi, O. Association of HLA-DRB1 and -DQ alleles and haplotypes with type 1 diabetes in Jordanians. Endocr. Metab. Immune Disord. Drug Targets, 2020, 20(6), 895-902.
[http://dx.doi.org/10.2174/1871530319666191119114031] [PMID: 31742498]
[57]
Bazzaz, J.T.; Amoli, M.M.; Taheri, Z.; Larijani, B.; Pravica, V.; Hutchinson, I.V. TNF-α and IFN-γ gene variation and genetic susceptibility to type 1 diabetes and its microangiopathic complications. J. Diabetes Metab. Disord., 2014, 13(1), 46.
[http://dx.doi.org/10.1186/2251-6581-13-46] [PMID: 24693923]
[58]
Allam, G.; Nasr, A.; Talaat, I.M.; Abuelsaad, A.S.A.; Bakheit, A.M.; Nemenqani, D.; Alsulaimani, A.A. Association between cytokine genes polymorphisms and type 1 diabetes: A case-control study on Saudi population. Immunol. Invest., 2018, 47(3), 229-240.
[http://dx.doi.org/10.1080/08820139.2017.1416398] [PMID: 29257900]
[59]
Guzmán-Flores, J.M.; Muñoz-Valle, J.F.; Sánchez-Corona, J.; Cobián, J.G.; Medina-Carrillo, L.; García-Zapién, A.G.; Cruz-Quevedo, E.G.; Flores-Martínez, S.E. Tumor necrosis factor-alpha gene promoter -308G/A and -238G/A polymorphisms in Mexican patients with type 2 diabetes mellitus. Dis. Markers, 2011, 30(1), 19-24.
[http://dx.doi.org/10.1155/2011/360312] [PMID: 21508505]
[60]
Boraska, V.; Rayner, N.W.; Groves, C.J.; Frayling, T.M.; Diakite, M.; Rockett, K.A.; Kwiatkowski, D.P.; Day-Williams, A.G.; McCarthy, M.I.; Zeggini, E. Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes. BMC Med. Genet., 2010, 11, 1-7.
[http://dx.doi.org/10.1186/1471-2350-11-69]
[61]
Khamees, M.; Jarrar, Y.; Al-Qirim, T.; Mahmoud, I.S.; Hatmal, M.M.; Alshaer, W.; Lee, S.J. No impact of soluble epoxide hydrolase rs4149243, rs2234914 and rs751142 genetic variants on the development of type II diabetes and its hypertensive complication among Jordanian patients. Int. J. Clin. Pract., 2021, 75(5), e14036.
[http://dx.doi.org/10.1111/ijcp.14036] [PMID: 33512081]

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