Nitric Oxide Synthase 2 Polymorphisms (rs2779248T/C and rs1137933C/T) and the Risk of Type 2 Diabetes in Zahedan, Southeastern Iran

  • Yasaman GARME Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
  • Mahdiyeh MOUDI Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
  • Ramin SARAVANI 1. Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran 2. Dept. of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
  • Hamidreza GALAVI 1. Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran 2. Dept. of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
Keywords: Type 2 diabetes mellitus, Single nucleotide polymorphism, Nitric oxide synthase type II, Inducible nitric oxide synthase

Abstract

Abstract Background: Nitric oxide (NO) has been associated with insulin resistance and type 2 diabetes (T2D). NO is synthesized enzymatically from l-arginine (l-Arg) by three NO synthase (NOS) isoforms, Neuronal NOS (nNOS or NOS1), Inducible NOS (iNOS or NOS2), and Endothelial NOS (eNOS or NOS3). The impact of NOS2 gene polymorphism was investigated on the susceptibility of T2D in a sample of Iranian population (Southeastern of Iran). Methods: In 2015, the present case-control study was conducted on 152 T2D patients and 157 healthy control subjects (HCs) referring to Bu-ali Hospital of Zahedan, eastern Iran. Genotyping of NOS2 rs2779248T/C and rs1137933C/T variants were done using the Tetra-Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-ARMS PCR) method. Results: CT genotype of rs1137933C/T was significantly associated with increased risk of T2D (P<0.0001). The T allele of this single nucleotide polymorphism (SNP) was also strongly associated with T2D risk (P<0.0001). For rs2779248 T/C, TC genotype of this SNP decreased the risk of T2D (OR=0.25 95%CI= 0.15-0.42, P<0.0001); however, CC genotype of this SNP increased the risk of T2D (P<0.005). There was no significant association between clinical-demographic characteristics of T2D group with respect to both SNPS in dominant. Conclusion: CT genotype and C allele of NOS2 rs1137933 C/T polymorphism were associated with a higher risk of T2D, and no association was observed between T allele of NOS2 rs2779248 T/C polymorphism and T2D while TC genotype of this SNP decreased the risk of T2D in the study participants.  

References

1. Gavin III JR, Alberti K, Davidson MB, DeFronzo RA (1997). Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care, 20:1183-1197.
2. Khoury MJ, Valdez R, Albright A (2008). Public health genomics approach to type 2 diabetes. Diabetes, 57:2911-2914.
3. Tibbs TL, Haire-Joshu D (2002). Avoiding high-risk behaviors: smoking prevention and cessation in diabetes care. Diabetes Spectr, 15:164-169.
4. Saravani S, Miri H, Saravani R et al (2015). Association of catalase (rs7943316) and glutathione peroxidase-1 (rs1050450) polymorphisms with the risk of type 2 diabetes (T2DM). Mol Genet Microbiol Virol, 30:216-220.
5. Inzucchi S, Bergenstal R, Fonseca V et al (2010). American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care, 33(Suppl 1): S62–S69.
6. Saravani R, Irani Z, Galavi HR (2016). Evaluation of transcription factor 7 like 2 polymorphisms and haplotypes in risk of type 2 diabetes. Rev Romana Med Lab, 24:423-430.
7. Shi Y, Hu FB (2014). The global implications of diabetes and cancer. Lancet, 383:1947-1948.
8. Vos T, Flaxman AD, Naghavi M et al (2012). Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 380:2163-2196.
9. Risérus U, Willett WC, Hu FB (2009). Dietary fats and prevention of type 2 diabetes. Prog Lipid Res, 48:44-51.
10. Galavi HR, Saravani R, Alamdari AR et al (2016). Evaluating the Effect of the rs2229238 and the rs4845625 Interleukin 6 Receptor Gene Polymorphisms on Body Mass Index and the Risk of Type 2 Diabetes in an Iranian Study Population. Int J High Risk Behav Addict, 5(4): e33289.
11. Luo T, Zhao Y, Li G et al (2001). A genome-wide search for type II diabetes susceptibility genes in Chinese Hans. Diabetologia, 44:501-506.
12. Xiang K, Wang Y, Zheng T et al (2004). Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24. Diabetes, 53:228-234.
13. Pincus G, White P (1934). On the inheritance of diabetes mellitus: ii. Further analysis of family histories. Am J Med Sci, 188:159-169.
14. Kobberling J, Tillil H (1982). Empirical risk figures for first degree relatives of non-insulin dependent diabetics. In: The genetics of diabetes mellitus. London: Academic Press; pp. 201–209.
15. Kahn M, C Ronald, Vicent M et al (1996). Genetics of non-insulin-dependent (type-II) diabetes mellitus. Annu Rev Med, 47:509-531.
16. Rich SS (1990). Mapping genes in diabetes: genetic epidemiological perspective. Diabetes, 39:1315-1319.
17. Rimoin DL, Connor JM, Pyeritz RE, Korf BR (2007). Emery and Rimoin's principles and practice of medical genetics. ed. Churchill Livingstone Elsevier.
18. Lindgren CM, McCarthy MI (2008). Mechanisms of disease: genetic insights into the etiology of type 2 diabetes and obesity. Nat Clin Pract Endocrinol Metab, 4:156-163.
19. Knowles RG, Moncada S (1994). Nitric oxide synthases in mammals. Biochem J, 298 ( Pt 2):249-58.
20. Xu W, Charles IG, Liu L et al (1996). Molecular cloning and structural organization of the human inducible nitric oxide synthase gene (NOS2). Biochem Biophys Res Commu, 219:784-788.
21. Sarginson JE, Deakin JW, Anderson IM et al (2014). Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk. Neuropsychopharmacology, 39:2857-2866.
22. Delli MN, Tirabassi G, Lamonica G et al (2015). Diabetes mellitus and late-onset hypogonadism: the role of Glu298Asp endothelial nitric oxide synthase polymorphism. Andrologia, 47:867-871.
23. Chand S, Chue CD, Edwards NC et al (2015). Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease. PloS One, 10:e0116160.
24. Luo J-Q, Wen J-G, Zhou H-H et al (2014). Endothelial nitric oxide synthase gene G894T polymorphism and myocardial infarction: a meta-analysis of 34 studies involving 21068 subjects. PLoS One, 9:e87196.
25. Qidwai T, Jamal F (2010). Inducible nitric oxide synthase (iNOS) gene polymorphism and disease prevalence. Scand J Immunol, 72:375-387.
26. Varadé J, Lamas JR, Fernández-Arquero M et al (2009). NO role of NOS2A susceptibility polymorphisms in rheumatoid arthritis. Nitric Oxide, 21:171-174.
27. Martín MC, Martinez A, Mendoza JL et al (2007). Influence of the inducible nitric oxide synthase gene (NOS2A) on inflammatory bowel disease susceptibility. Immunogenetics, 59:833-837.
28. Chen F, Li YM, Yang LQ et al (2016). Association of NOS2 and NOS3 gene polymorphisms with susceptibility to type 2 diabetes mellitus and diabetic nephropathy in the Chinese Han population. IUBMB Life, 68(7):516-25.
29. Manna I, Liguori M, Valentino P et al (2011). NOS2A as a candidate gene in Relapsing–Remitting Multiple Sclerosis: A haplotype study using selected subsets of single nucleotide polymorphisms. J Neurol Sci, 304:75-77.
30. Saravani R, Galavi HR, Ranjbar N, Alamdari AR (2017). ATP-Binding Cassette Transporter A1 Polymorphisms and Haplotypes in Risk of Type 2 Diabetes. Gene, Cell and Tissue, 4(1): e13326.
31. Saravani S, Yari D, Saravani R, Ahmadabadi CA (2017). Association of COL4A3 (rs55703767), MMP‑9 (rs17576) and TIMP‑1 (rs6609533) gene polymorphisms with susceptibility to type 2 diabetes. Biomed Rep, 6(3):329-34.
32. Mousavi M, Saravani R, Modrek MJ et al (2016). Detection of Toxoplasma gondii in Diabetic Patients Using the Nested PCR Assay via RE and B1 Genes. Jundishapur J Microbiol, 9(2): e29493.
33. Tremblay K, Daley D, Chamberland A et al (2008). Genetic variation in immune signaling genes differentially expressed in asthmatic lung tissues. J Allergy Clin Immunol, 122:529-36.e17.
34. Zhang J, Li B, Ding X et al (2014). Genetic variants in inducible nitric oxide synthase gene are associated with the risk of radiation-induced lung injury in lung cancer patients receiving definitive thoracic radiation. Radiother Oncol, 111:194-198.
35. Payton A, Payne D, Mankhambo LA et al (2009). Nitric oxide synthase 2A (NOS2A) polymorphisms are not associated with invasive pneumococcal disease. BMC Med Genet, 10:28.
36. Bind M-A, Coull B, Suh H et al (2014). A novel genetic score approach using instruments to investigate interactions between pathways and environment: application to air pollution. PloS One, 9:e96000.
37. Levinsson A (2015). Interaction of genetic susceptibility and traffic-related air pollution in cardiovascular disease. https://gupea.ub.gu.se/bitstream/2077/37531/2/gupea_2077_37531_2.pdf
38. Donath MY, Shoelson SE (2011). Type 2 diabetes as an inflammatory disease. Nat Rev Immunol, 11:98-107.
39. Dhillon SS, Mastropaolo LA, Murchie R et al (2014). Higher activity of the inducible nitric oxide synthase contributes to very early onset inflammatory bowel disease. Clin Transl Gastroenterol, 5:e46.
Published
2018-11-01
How to Cite
1.
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. IJPH. 47(11):1734-41.
Section
Original Article(s)