Vol 10, No 5 (2021)
Research paper
Published online: 2021-05-24

open access

Page views 6406
Article views/downloads 278
Get Citation

Connect on Social Media

Connect on Social Media

The relation between IL-10 gene (-1082G/A) and VEGF gene 936 C/T polymorphism and diabetic polyneuropathy in a cohort of Egyptian patients with type 2 diabetes

Salma Alaa Eldin Imbaby1, Mai Badrah1, Yousra Hisham Abdel-Fattah1
Clin Diabetol 2021;10(5):420-427.

Abstract

Background: Polymorphisms have been described to correlate with T2DM and its complications including diabetic polyneuropathy (DPN). The aim of this study was to investigate the relation between interleukin (IL)-10-1082 G/A and vascular endothelial growth factor (VEGF)-936 C/T polymorphism and DPN in type 2 diabetes mellitus (T2DM) patients. Methods: This cross-sectional study included 50 T2DM patients and 40 controls. Clinical and electrophysiological assessments for DPN, fasting blood glucose level (FBS) and glycosylated haemoglobin (Hb A1C) were recorded. VEGF-936 C/T polymorphism was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotyping for IL-10 promotor gene (-1082 G/A) polymorphism was performed using Real-time PCR. Results: Sixty percent of patients had confirmed DPN, while none were considered normal. IL-10 (genotype -1082G/G) was statistically higher among controls compared to patients (p=0.008). VEGF-936-CT genotype was statistically higher among patients compared to controls (p=0.033), but there was no significant relation between IL-10-1082 G/A or VEGF-936 C/T polymorphism genotypes and DPN. IL-10 (genotype -1082A/G) had higher HbA1C levels (p=0.041) and a lower albumin/creatinine ratio, while IL-10 (genotype -1082G/G) had a higher albumin/creatinine ratio (p=0.024). DPN had a significant correlation with duration of diabetes, FBS and HbA1C. Conclusion: The VEGF-936 C/T genotype may be associated with T2DM, while the IL-10 (genotype -1082G/G) may be less likely to be associated with it; however there was no association between VEGF-936 or IL-10-1082 genotypes and DPN.

Article available in PDF format

View PDF Download PDF file

References

  1. Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care. 2004; 27(3): 813–823.
  2. Okemah J, Peng J, Quiñones M. Addressing Clinical Inertia in Type 2 Diabetes Mellitus: A Review. Adv Ther. 2018; 35(11): 1735–1745.
  3. Cieślak M, Cieślak M. Role of purinergic signalling and proinflammatory cytokines in diabetes. Clinical Diabetology. 2017; 6(3): 90–100.
  4. Tesfaye S, Selvarajah D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev. 2012; 28 Suppl 1: 8–14.
  5. Juster-Switlyk K, Smith AG. Updates in diabetic peripheral neuropathy. F1000Res. 2016; 5.
  6. Elkhamisy E, Khalel M, Elbioumy A, et al. Beta-endorphin levels in both painful and painless diabetic peripheral neuropathy and its relations to pain characters and severity. Clinical Diabetology. 2017; 6(5): 159–171.
  7. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006; 116(7): 1793–1801.
  8. Donath MY, Størling J, Maedler K, et al. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med (Berl). 2003; 81(8): 455–470.
  9. Bidwell J, Keen L, Gallagher G, et al. Cytokine gene polymorphism in human disease: on-line databases. Genes Immun. 1999; 1(1): 3–19.
  10. Kolla VK, Madhavi G, Pulla Reddy B, et al. 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.
  11. Lee JH, Lee W, Kwon OhH, et al. Cytokine profile of peripheral blood in type 2 diabetes mellitus patients with diabetic retinopathy. Ann Clin Lab Sci. 2008; 38(4): 361–367.
  12. Moore KW, de Waal Malefyt R, Coffman RL, et al. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19: 683–765.
  13. Lin MT, Storer B, Martin PJ, et al. Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med. 2003; 349(23): 2201–2210.
  14. Tarabay M, Elshazli R, Settin A. African vs. Caucasian and Asian difference for the association of interleukin-10 promotor polymorphisms with type 2 diabetes mellitus (a meta-analysis study). Meta Gene. 2016; 9: 10–17.
  15. Thanigaimani S, Kichenadasse G, Mangoni AA. The emerging role of vascular endothelial growth factor (VEGF) in vascular homeostasis: lessons from recent trials with anti-VEGF drugs. Curr Vasc Pharmacol. 2011; 9(3): 358–380.
  16. Yang B, Cross DF, Ollerenshaw M, et al. Polymorphisms of the vascular endothelial growth factor and susceptibility to diabetic microvascular complications in patients with type 1 diabetes mellitus. J Diabetes Complications. 2003; 17(1): 1–6.
  17. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37 Suppl 1: S81–S90.
  18. Meijer JWG, Smit AJ, Sonderen EV, et al. Symptom scoring systems to diagnose distal polyneuropathy in diabetes: the Diabetic Neuropathy Symptom score. Diabet Med. 2002; 19(11): 962–965.
  19. Preston D, Shapiro B. Clinical–Electrophysiologic Correlations. Electromyography and Neuromuscular Disorders. 2013: 249–266.
  20. Cavaletti G, Frigeni B, Lanzani F, et al. Italian NETox Group. The Total Neuropathy Score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity: comparison with the National Cancer Institute-Common Toxicity Scale. J Peripher Nerv Syst. 2007; 12(3): 210–215.
  21. Dyck PJ, Carter RE, Litchy WJ. Modeling nerve conduction criteria for diagnosis of diabetic polyneuropathy. Muscle Nerve. 2011; 44(3): 340–345.
  22. DYCK P, HUGHES R, O'BRIEN P. Quantitating Overall Neuropathic Symptoms, Impairments, and Outcomes. Peripheral Neuropathy. 2005: 1031–1051.
  23. Dyck PJ, Albers JW, Andersen H, et al. Toronto Expert Panel on Diabetic Neuropathy. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev. 2011; 27(7): 620–628.
  24. Krippl P, Langsenlehner U, Renner W, et al. A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk. Int J Cancer. 2003; 106(4): 468–471.
  25. Barus J, Setyopranoto I, Sadewa AH, et al. Gene Polymorphism in Indonesian Subjects with Diabetic Polyneuropathy. Open Access Maced J Med Sci. 2018; 6(10): 1784–1789.
  26. Hua Y, Shen J, Song Y, et al. Interleukin-10 -592C/A, -819C/T and -1082A/G Polymorphisms with Risk of Type 2 Diabetes Mellitus: A HuGE Review and Meta-analysis. PLoS One. 2013; 8(6): e66568.
  27. Liu L, Zheng J, Xu Y, et al. Association between interleukin-10 gene rs1800896 polymorphism and diabetic retinopathy in a Chinese Han population. Biosci Rep. 2019; 39(4).
  28. Ghisleni MM, Biolchi V, Jordon BC, et al. Association study of C936T polymorphism of the VEGF gene and the C242T polymorphism of the p22phox gene with diabetes mellitus type 2 and distal diabetic polyneuropathy. Mol Med Rep. 2015; 12(3): 4626–1633.
  29. Motawi TK, Rizk SM, Ibrahim IAR, et al. Alterations in circulating angiogenic and anti-angiogenic factors in type 2 diabetic patients with neuropathy. Cell Biochem Funct. 2014; 32(2): 155–163.
  30. Costa PZ, Soares R. Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox. Life Sci. 2013; 92(22): 1037–1045.
  31. Kim HW, Ko GJ, Kang YS, et al. Role of the VEGF 936 C/T polymorphism in diabetic microvascular complications in type 2 diabetic patients. Nephrology (Carlton). 2009; 14(7): 681–688.
  32. Tavakkoly-Bazzaz J, Amoli MM, Pravica V, et al. VEGF gene polymorphism association with diabetic neuropathy. Mol Biol Rep. 2010; 37(7): 3625–3630.
  33. Peltier A, Goutman SA, Callaghan BC. Painful diabetic neuropathy. BMJ. 2014; 348: g1799.