AB0077 ASSOCIATION BETWEEN VITAMIN D RECEPTOR GENE POLYMORPHISMS AND SYSTEMIC LUPUS ERYTHEMATOSUS IN MALTESE PATIENTS
Authors: R. Magro, J. A. Grech Meli, J. Debattista, N. Aquilina, K. Gatt, A. Borg, C. Scerri
Journal: Annals of the Rheumatic Diseases (2021)

Background: Vitamin D deficiency is highly prevalent in patients with systemic lupus erythematosus (SLE). Vitamin D acts through the vitamin D receptor (VDR) that is present in most cells, and it can regulate the transcription of over 200 genes. The expression of vitamin D receptors by a variety of cells belonging to the innate and adaptive immune systems has created interest with regards to the role of vitamin D in the pathogenesis of SLE. Several polymorphisms of the VDR gene have been described, namely Bsml, Apal, Taql and Fokl. A number of VDR gene polymorphism genotypes have been associated with increased risk of SLE mostly in Asians and Africans. 1 Objectives: The aim of this study was to establish whether an association was present between VDR gene polymorphisms and SLE susceptibility in a cohort of SLE patients living in Malta. A further aim was to assess the relationship between these VDR gene polymorphisms and SLE disease characteristics. Methods: 59 SLE patients living in Malta and attending Rheumatology clinic at Mater Dei Hospital were recruited for the study after providing informed consent. The patients were over the age of 18 years and fulfilled the SLICC classification criteria for SLE. The patients were interviewed and blood samples were taken. RNA extraction was performed from whole blood. QuantiGene Plex technology was used to measure the expression of 12 interferon (IFN) signature genes in the extracted RNA. 93 cord blood samples obtained from individuals living in Malta were used as a control. DNA extraction was carried out from the blood samples obtained from the patients and controls. The VDR gene was screened and the regions containing the VDR polymorphisms were amplified for each patient. The amplified regions were then digested with their respective restriction enzymes in order to view the patient’s genotype via restriction fragment length polymorphism. Statistical analysis, including odds ratio (OR), was carried out to gauge the significance in the association of these polymorphisms with SLE. Results: 94.9% of SLE patients were female and they had a mean age of 44.5 years. All the patients were of Caucasian ethnicity. 13.6% had vitamin D deficiency (serum 25-hydroxyvitamin D &lt;20ng/ml) and 25.4% were vitamin D insufficient (serum 25-hydroxyvitamin D 20-29ng/ml). The results showed that when ApaI polymorphism was present as a homozygote for the variant allele there was a significant decrease in SLE prevalence (OR=0.39, CI 0.17-0.87, p=0.02). The results were also analysed by placing the polymorphs into haplotypes. The haplotype containing all wild-type alleles for the VDR gene and the haplotype containing all wild-type alleles with the variant allele for FokI had an increased prevalence of SLE (OR= 1.95, CI 1.12-3.38, p=0.01 and OR= 2.36, CI 1.13-4.91, p=0.02 respectively). The patients who were homozygous for the variant allele for BsmI had a significantly higher SLE disease activity index-2K (SLEDAI-2K) (mean 5.00) compared to those that were heterozygous (mean 2.66; p=0.010). No significant difference was noted in damage, IFN signature gene expression, organ manifestation and autoantibody profile between the different genotypes for the 4 VDR polymorphisms. SLE patients who were homozygous variant for the ApaI or TaqI polymorphisms had an increased prevalence of fibromyalgia (OR=7.50, CI 1.47-38.16, p=0.02 and OR=12.00, CI 1.80-80.05, p=0.02 respectively). Conclusion: The study showed that in the Maltese population the presence of the VDR gene polymorphism haplotype containing all wild-type alleles and the haplotype containing all wild-type alleles with the variant allele for FokI are associated with an increased risk of SLE. Moreover the homozygous variant genotype for BsmI was associated with a higher SLE disease activity. The homozygous variant genotype for ApaI and TaqI was associated with a higher risk of fibromyalgia in SLE patients. References: [1]Zhou TB, Jiang ZP, Lin ZJ, Su N. Association of vitamin D receptor gene polymorphism with the risk of systemic lupus erythematosus. J Recept Signal Transduct Res. 2015;35(1):8-14. Acknowledgements: The Faculty of Medicine and Surgery, University of Malta provided funding for this research. Disclosure of Interests: None declared