Association of the rs3758391 polymorphism in the SIRT1 gene with diabetic nephropathy and decreased estimated glomerular filtration rate (GFR) in a population from southwest Iran

  • Ramin Tavakoli Faradonbeh
  • Mehrnoosh Zakerkish
  • Ali Karimi Akhormeh
  • Narges Mohammadtaghvaei
  • Mohammad Taha Jalali
  • Hamid YaghootiEmail author
Original Article



Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disorder. SIRT1 has an essential role in the insulin-signaling pathway and energy homeostasis. SIRT1 exerts protective effects in the kidney cells.


We aimed to investigate whether the rs3758391 variant was associated with diabetic nephropathy, measures of kidney function, and BMI in a population with and without diabetes in southwest Iran.


The study comprised 132 patients with type 2 diabetes mellitus (T2DM) (with and without nephropathy). They were compared with 66 normal subjects. The subjects were genotyped for the rs3758391 polymorphism by the PCR–RFLP method. Fasting blood glucose, HbA1c, urea, creatinine, and urinary albumin were measured using a biochemistry analyzer. Serum cystatin C levels were measured by ELISA.


The genotype distribution and allele frequencies were significantly different between the entirely diabetic group and the healthy subjects (p value < 0.05). For T2DM, the odds ratios (ORs) for the TT genotype and the T allele carrier were 5.7 (95% confidence interval (CI) 2.2–14.9, p < 0.001) and 4.01 (95% CI 2.1–7.5, p < 0.001), respectively. For diabetic nephropathy, the ORs for the TT genotype and the T allele carrier were 3.96 (95% CI 1.5–10.0, p = 0.003) and 3.0 (95% CI 1.4–6.4, p = 0.003), respectively. For decreased eGFR below 60 mL/min/1.73m2, the OR for TT was 2.9 (95% CI 1.1–7.5, p = 0.02).


Our results confirm that the risk allele of the rs3758391 SNP in the SIRT1 gene is strongly associated with T2DM and diabetic nephropathy. The TT genotype is also associated with decreased eGFR.


Type 2 diabetes Diabetic nephropathy SIRT1 rs3758391 polymorphism eGFR 



This paper is issued from the M.Sc. thesis of Ramin Tavakoli Faradonbeh.


This study is funded by Ahvaz Jundishapur University of Medical Sciences (Grant No. D-9501).

Compliance with ethical standards

Human and animal rights

The study has been approved by the appropriate local ethics committee at the Ahvaz Jundishapur University of Medical Sciences (IR.AJUMS.REC.1395.76) and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Ethical standard

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ahvaz Jundishapur University of Medical Sciences research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med. 1998;15(7):539–53.CrossRefGoogle Scholar
  2. 2.
    Florez JC. The genetics of type 2 diabetes: a realistic appraisal in 2008. J Clin Endocrinol Metab. 2008;93:4633–42. Scholar
  3. 3.
    Andersen AR, Christiansen JS, Andersen JR, Kreiner S, Deckert T. Diabetic nephropathy in type 1 insulin-dependent diabetes: an epidemiological study. Diabetologia. 1983;25(6):496–501.CrossRefGoogle Scholar
  4. 4.
    Collins AJ, Foley RN, Gilbertson DT, Chen SC. United States renal data system public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl (2011). 2015;5(1):2–7.CrossRefGoogle Scholar
  5. 5.
    Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR. The changing natural history of nephropathy in type I diabetes. Am J Med. 1985;78(5):785–94.CrossRefGoogle Scholar
  6. 6.
    Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977–86.CrossRefGoogle Scholar
  7. 7.
    UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854–65.CrossRefGoogle Scholar
  8. 8.
    Everett M. They say it runs in the family: diabetes and inheritance in Oaxaca, Mexico. Soc Sci Med. 2011;72:1776–83. Scholar
  9. 9.
    Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complication Trial. J Pediatr. 1994;125:177–88.CrossRefGoogle Scholar
  10. 10.
    Kelly G. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 1. Altern Med Rev. 2010;15(3):245–63.Google Scholar
  11. 11.
    Higashibata T, Wakai K, Naito M, Morita E, Hishida A, Hamajima N, et al. Effects of self-reported calorie restriction on correlations between SIRT1 polymorphisms and body mass index and long-term weight change. Gene. 2016;594:16–22. Scholar
  12. 12.
    Han J, Wei M, Wang Q, Li X, Zhu C, Mao Y, et al. Association of genetic variants of SIRT1 with type 2 diabetes mellitus. Gene Expr. 2015;16:177–85. Scholar
  13. 13.
    Maeda S, Koya D, Araki S, Babazono T, Umezono T, Toyoda M, et al. Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes. Clin Exp Nephrol. 2011;15:381–90. Scholar
  14. 14.
    Kume S, Uzu T, Horiike K, Chin-Kanasaki M, Isshiki K, Araki S, et al. Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest. 2010;120:1043–55. Scholar
  15. 15.
    Blander G, Guarente L. The Sir2 family of protein deacetylases. Annu Rev Biochem. 2004;73(1):417–35.CrossRefGoogle Scholar
  16. 16.
    Kitada M, Kume S, Takeda-Watanabe A, Kanasaki K, Koya D. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy. Clin Sci (Lond). 2013;124:153–64. Scholar
  17. 17.
    Cruz M, Valladares-Salgado A, Garcia-Mena J, Ross K, Edwards M, Angeles-Martinez J, et al. Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City. Diabetes Metab Res Rev. 2010;26:261, 270. Scholar
  18. 18.
    Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002;40(2):221–6.CrossRefGoogle Scholar
  19. 19.
    Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367:20–9. Scholar
  20. 20.
    Mohtavinejad N, Nakhaee A, Harati H, Poodineh J, Afzali M. SIRT1 gene is associated with cardiovascular disease in the Iranian population. Egyptian Journal of Medical Human Genetics. 2015;16(2):117–22.CrossRefGoogle Scholar
  21. 21.
    Schug TT, Li X. Sirtuin 1 in lipid metabolism and obesity. Ann Med. 2011;43:198–211. Scholar
  22. 22.
    Kitada M, Koya D. SIRT1 in type 2 diabetes: mechanisms and therapeutic potential. Diabetes Metab J. 2013;37:315–25. Scholar
  23. 23.
    Zheng J, Chen LL, Xiao F, Hu X, Deng X, Li H. Three single nucleotide variants of the SIRT1 gene are associated with overweight in a Chinese population: a case control study. Endocr J. 2012;59(3):229–37.CrossRefGoogle Scholar
  24. 24.
    Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isshiki K, et al. SIRT1 inhibits transforming growth factor β-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation. J Biol Chem. 2007;282(1):151–8.CrossRefGoogle Scholar
  25. 25.
    Yacoub R, Lee K, He JC. The role of SIRT1 in diabetic kidney disease. Front Endocrinol (Lausanne). 2014;5.

Copyright information

© Research Society for Study of Diabetes in India 2019

Authors and Affiliations

  • Ramin Tavakoli Faradonbeh
    • 1
    • 2
  • Mehrnoosh Zakerkish
    • 2
  • Ali Karimi Akhormeh
    • 1
  • Narges Mohammadtaghvaei
    • 3
  • Mohammad Taha Jalali
    • 3
  • Hamid Yaghooti
    • 1
    • 3
    Email author
  1. 1.Department of Medical Laboratory Sciences, School of Allied Medical SciencesAhvaz Jundishapur University of Medical SciencesAhvazIran
  2. 2.Diabetes Research Center, Health Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran
  3. 3.Hyperlipidemia Research Center, Department of Medical Laboratory Sciences, School of Allied Medical SciencesAhvaz Jundishapur University of Medical SciencesAhvazIran

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