The Relationship Between Cigarette Smoking, NOS3 Gene T-786→C Polymorphism, and Diabetic Nephropathy


avatar Sayed Alireza Mirsane 1 , 2 , * , avatar Shima Shafagh 3 , avatar Nasrin Oraei 4

Genetic Sciences Student, Qom, IR Iran
Surgical Technologist, Kashan University of Medical Sciences, Kashan, Iran
General Surgery Specialist, Kashan University of Medical Sciences, Kashan, Iran
Lecturer of Islamic Sciences, Education office, Esfahan, Iran

how to cite: Mirsane S A, Shafagh S, Oraei N. The Relationship Between Cigarette Smoking, NOS3 Gene T-786→C Polymorphism, and Diabetic Nephropathy. Gene Cell Tissue. 2017;4(2):e45302. doi: 10.5812/gct.45302.

Dear Editor,

Gene polymorphism can cause serious problems for humans. Endothelial nitric oxide synthase (NOS3) gene is one of the important human genes, which plays a significant role in normal endothelial function; consequently, polymorphism of this gene can cause vascular diseases in diabetic patients (1, 2). On the other hand, smoking can contribute to increased T-786→C polymorphism of NOS3 gene, and more importantly, -786C allele can increase the harmful effects of smoking (3).

Diabetic nephropathy (DN) is a cardiovascular disease in patients with type II diabetes. Numerous studies have been conducted on the relationship between T-786→C polymorphism and DN. In this regard, researchers have stated that C allele for T-786→C polymorphism is more common among patients with diabetes and DN, compared to those without DN. In fact, the outbreak is so severe that this polymorphism was introduced as a risk factor for increasing DN in diabetic patients (2).

Also, Ahluwalia et al. stated that risk of DN is associated with (-786)CC genotype. They indicated that T-786→C functional polymorphism of NOS3 gene could lead to reduced gene expression of NOS3 (4). In addition, another study suggested a significant and interesting relationship between (-786)C allele and increasing risk of DN. This study was performed on Japanese diabetic patients, and it was revealed that T-786→C polymorphism could intervene in the progress of DN (5). On the other hand, in a meta-analysis, it was concluded that this polymorphism is associated with susceptibility to DN (6). Also, Mooyaart et al. confirmed this findings in another meta-analysis (7).

As mentioned earlier, it can be understood that T-786→C polymorphism is an important factor for DN, and as stated, smoking is a developing and progressing risk factor for any problem in this polymorphism; therefore, T-786→C polymorphism and smoking are 2 serious risk factors for diabetes. Smoking is not permitted for either diabetic or nondiabetic patients. In fact, due to increased probability of serious health problems in diabetic patients, smoking should be avoided, as it is associated with DN. Overall, diabetic patients or those at risk can promote their health by avoiding smoking.


  • 1.

    Mirsane SA, Shafagh S. The Relationship Between XRCC1 Arg399Gln polymorphism, alcohol consumption and colorectal cancer: one of the alcohol forbidding reasons in Islam. Gene Cell Tissue. 2016; 3 (3)[DOI]

  • 2.

    Shoukry A, Shalaby SM, Abdelazim S, Abdelazim M, Ramadan A, Ismail MI, et al. Endothelial nitric oxide synthase gene polymorphisms and the risk of diabetic nephropathy in type 2 diabetes mellitus. Genet Test Mol Biomarkers. 2012; 16 (6) : 574 -9 [DOI][PubMed]

  • 3.

    Misiak B, Krolik M, Kukowka A, Lewera A, Leszczynski P, Stankiewicz-Olczyk J, et al. The Role of -786T/C Polymorphism in the Endothelial Nitric Oxide Synthase Gene in Males with Clinical and Biochemical Features of the Metabolic Syndrome. Int J Endocrinol. 2011; 2011 : 458750 [DOI][PubMed]

  • 4.

    Ahluwalia TS, Ahuja M, Rai TS, Kohli HS, Sud K, Bhansali A, et al. Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians. Mol Cell Biochem. 2008; 314 (1-2) : 9 -17 [DOI][PubMed]

  • 5.

    Asakimori Y, Yorioka N, Taniguchi Y, Ito T, Ogata S, Kyuden Y, et al. T(-786)-->C polymorphism of the endothelial nitric oxide synthase gene influences the progression of renal disease. Nephron. 2002; 91 (4) : 747 -51 [DOI][PubMed]

  • 6.

    He Y, Fan Z, Zhang J, Zhang Q, Zheng M, Li Y, et al. Polymorphisms of eNOS gene are associated with diabetic nephropathy: a meta-analysis. Mutagenesis. 2011; 26 (2) : 339 -49 [DOI][PubMed]

  • 7.

    Mooyaart AL, Valk EJ, van Es LA, Bruijn JA, de Heer E, Freedman BI, et al. Genetic associations in diabetic nephropathy: a meta-analysis. Diabetologia. 2011; 54 (3) : 544 -53 [DOI][PubMed]

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