Sirtuin 1 rs7069102 polymorphism is associated with diabetic nephropathy in patients with type 2 diabetes mellitus

Jernej Letonja; Matej Završnik; Jana Makuc; Maja Šeruga; Ana Peterlin; Ines Cilenšek; Danijel Petrovič

doi:10.17305/bjbms.2020.5368

Authors

Jernej Letonja Institute of Histology and Embryology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0002-1473-3534
Matej Završnik Department for diabetes and metabolic diseases, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia https://orcid.org/0000-0002-2881-9363
Jana Makuc Department of Internal Medicine, General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia https://orcid.org/0000-0002-4201-5054
Maja Šeruga Department of Internal Medicine, General Hospital Murska Sobota, Murska Sobota, Slovenia https://orcid.org/0000-0001-6769-6610
Ana Peterlin Institute of Histology and Embryology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0001-8728-2298
Ines Cilenšek Institute of Histology and Embryology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0002-1702-7715
Danijel Petrovič Institute of Histology and Embryology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0001-6637-2542

DOI:

https://doi.org/10.17305/bjbms.2020.5368

Keywords:

SIRT1, rs7069102, diabetic nephropathy, type 2 diabetes mellitus, association study

Abstract

The global prevalence for diabetes mellitus nearly doubled from 4.7% in 1980 to 8.5% in 2014. Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that is expressed in a variety of tissues. It modifies proteins that participate in DNA repair, stress, and inflammatory response. The aim of the study was to investigate the relationship between SIRT1 rs7069102 polymorphism and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). In our retrospective association study, we included 724 Slovene (Caucasian) patients who have had T2DM for at least 10 years. We classified the participants into two groups, the first group was comprised of 301 patients with DN, and the second (control) group was comprised of 423 patients without DN. We analyzed the rs7069102 polymorphism using StepOne real-time polymerase chain reaction (PCR) System and TaqMan SNP Genotyping Assay. We found a statistically significant difference in the distribution of rs7069102 genotypes and alleles between the two groups. We used logistic regression analysis and adjusted for systolic pressure, arterial hypertension (AH), duration of AH, triglycerides, the value of HbA1c, carotid disease, diabetic foot, and diabetic retinopathy. Furthermore, we discovered that patients with the CC genotype are significantly more likely to develop DN according to both the codominant (odds ratio [OR] = 1.94; 95% confidence interval [CI] = 1.09-3.45; p = 0.02) and recessive (OR = 2.39; 95% CI = 1.12-5.08; p = 0.02) models of inheritance. We found a significant association between the SIRT1 rs7069102 polymorphism and DN in T2DM. We speculate that SIRT1 rs7069102 might be an interesting marker of DN.