Vitamin D attenuates elevated oxidative DNA damage in scleroderma patients with organ involvement: A prospective study

• Published in: The Journal of steroid biochemistry and molecular biology 2023-05, Vol.229, p.106273-106273, Article 106273
• Main Authors: Dal-Bekar, Nazlı Ecem, İşlekel, Gül Hüray, Köken-Avşar, Aydan, Yarkan-Tuğsal, Handan, Tuna, Gamze, Zengin, Berrin, Birlik, Ahmet Merih
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2'-Deoxyguanosine; Case-Control Studies; Chromatography, Liquid; Genetic Predisposition to Disease; Genotype; Humans; Mass spectrometry; Oxidative DNA damage; Oxidative Stress; Polymorphism, Single Nucleotide; Prospective Studies; Receptors, Calcitriol - genetics; Systemic sclerosis; Tandem Mass Spectrometry; Vitamin D; Vitamin D receptor; Vitamins - pharmacology; Vitamins - therapeutic use
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2023.106273

Scleroderma is a rare autoimmune disease characterized by progressive fibrosis of the skin and internal organs. Oxidative damage to macromolecules has been reported to occur in scleroderma. Among the macromolecular damages, oxidative DNA damage is a sensitive and cumulative marker of oxidative stress and is of particular interest because of its cytotoxic and mutagenic effects. Vitamin D supplementation is an important part of treatment, as vitamin D deficiency is a common problem in scleroderma. Furthermore, the antioxidant role of vitamin D has been demonstrated in recent studies. In light of this information, the present study aimed to comprehensively investigate oxidative DNA damage in scleroderma at baseline and to evaluate the contribution of vitamin D supplementation to the attenuation of DNA damage in a prospectively designed study. In accordance with these objectives, oxidative DNA damage in scleroderma was evaluated by measurement of stable damage products (8-oxo-dG, S-cdA, and R-cdA) in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS); serum vitamin D levels were determined by high-resolution mass spectrometry (HR-MS); VDR gene expression and four polymorphisms in the VDR gene (rs2228570, rs1544410, rs7975232, and rs731236) were analyzed by RT-PCR and compared with healthy subjects. In the prospective part, the DNA damage and the VDR expression of the patients who received vitamin D were re-evaluated after the replacement. As a result of this study, we demonstrated that all DNA damage products were increased in scleroderma patients compared to healthy controls, whereas vitamin D levels and VDR expression were significantly lower (p