SLC22A3 rs2048327 polymorphism is associated with diabetic retinopathy in caucasians with type 2 diabetes mellitus

Grbić, Emin (author), Globočnik Petrovič, Mojca (author), Cilenšek, Ines (author), Petrovič, Danijel (author)

The Solute Carrier Family 22 Member 3 (SLC22A3) is a high-capacity, low-affinity transporter for the neurotransmitters norepinephrine, epinephrine, dopamine, serotonin, and histamine. SLC22A3 plays important roles in interorgan and interorganism small-molecule communication, and also regulates local and overall homeostasis in the body. Our aim was to investigate the association between the rs2048327 gene polymorphism and diabetic retinopathy (DR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated SLC22A3 expression in the fibrovascular membranes (FVMs) of patients with proliferative DR (PDR). Our study involved 1555 unrelated Caucasians with T2DM with a defined ophthalmologic status: 577 of them with DR as the study group, and 978 without DR as the control group. The investigated polymorphisms were genotyped using the KASPar genotyping assay. The expression of SLC22A3 (organic cation transporter 3-OCT3) was examined via immunohistochemistry in human FVM from 16 patients with PDR. The C allele and CC genotype frequencies of the rs2048327 polymorphism were significantly higher in the study group compared to the controls. The logistic regression analysis showed that the carriers of the CC genotype in the recessive genetic models of this polymorphism have a 1.531-fold increase (95% CI 1.083-2.161) in the risk of developing DR. Patients with the C allele of rs2048327 compared to the homozygotes for the wild type T allele exhibited a higher density of SLC22A3 (OCT3)-positive cells (10.5 ± 4.5/mm2 vs. 6.1 ± 2.7/mm2, respectively; p < 0.001). We showed the association of the rs2048327 SLC22A3 gene polymorphism with DR in a Slovenian cohort with type 2 diabetes mellitus, indicating its possible role as a genetic risk factor for the development of this diabetic complication.

• Language: English
• Keywords: SLC22A3, diabetic retinopathy, immunohistochemistry, rs2048327
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 10
• Numbering: Vol. 11, iss. 8, art. 2303
• PID: 20.500.12556/RUL-185504
• UDC: 611
• ISSN on article: 2227-9059
• DOI: 10.3390/biomedicines11082303
• COBISS.SI-ID: 162362371
• Publication date in RUL: 07.08.2026

Record is a part of a journal

• Title: Biomedicines
• Shortened title: Biomedicines
• Publisher: MDPI AG
• ISSN: 2227-9059
• COBISS.SI-ID: 523006745

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: diabetična retinopatija, imunohistokemija

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0326
• Name: Ginekologija in reprodukcija: Genomika za personalizirano medicino