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
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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.
KeywordsType 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.
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 was obtained from all individual participants included in the study.
Conflict of interest
The authors declare that they have no conflict of interest.
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