Grbić Emin, Globočnik Petrovič Mojca, Cilenšek Ines, Petrovič Danijel
Department of Physiology, Faculty of Medicine, University of Tuzla, 75000 Tuzla, Bosnia and Herzegovina.
Clinic of Ophthalmology, Ljubljana University Medical Centre, 1000 Ljubljana, Slovenia.
Biomedicines. 2023 Aug 18;11(8):2303. doi: 10.3390/biomedicines11082303.
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/mm vs. 6.1 ± 2.7/mm, respectively; < 0.001). We showed the association of the rs2048327 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.
溶质载体家族22成员3（SLC22A3）是去甲肾上腺素、肾上腺素、多巴胺、血清素和组胺等神经递质的一种高容量、低亲和力转运体。SLC22A3在器官间和生物间小分子通讯中发挥重要作用，还调节体内局部和整体的稳态。我们的目的是研究斯洛文尼亚2型糖尿病（T2DM）患者中rs2048327基因多态性与糖尿病视网膜病变（DR）之间的关联。我们还研究了增殖性DR（PDR）患者纤维血管膜（FVMs）中SLC22A3的表达。我们的研究纳入了1555名无亲缘关系的白种T2DM患者，他们具有明确的眼科状况：其中577名患有DR作为研究组，978名无DR作为对照组。使用KASPar基因分型检测对所研究的多态性进行基因分型。通过免疫组织化学检测了16例PDR患者人FVM中SLC22A3（有机阳离子转运体3 - OCT3）的表达。与对照组相比，研究组中rs2048327多态性的C等位基因和CC基因型频率显著更高。逻辑回归分析表明，在该多态性的隐性遗传模型中，CC基因型携带者发生DR的风险增加1.531倍（95%可信区间1.083 - 2.161）。与野生型T等位基因纯合子相比，rs2048327 C等位基因患者的SLC22A3（OCT3）阳性细胞密度更高（分别为10.5±4.5/mm与6.1±2.7/mm；P<0.001）。我们在斯洛文尼亚2型糖尿病队列中显示了rs2048327基因多态性与DR的关联，表明其可能作为这种糖尿病并发症发生的遗传危险因素。
