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Background/Aims Vitamin D deficiency is highly prevalent in systemic lupus erythematosus (SLE) patients, most likely due to sun avoidance. 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 (rs1544410), Apal (rs7975232), Taql(rs731236) and Fokl (rs2228570). A number of VDR gene polymorphisms have been associated with increased risk of SLE mostly in Asians and Africans. The aim of this study was to establish whether an association was present between VDR gene polymorphisms (Bsml, Apal, Taql and Fokl) and SLE susceptibility in a cohort of SLE patients living in Malta. Methods 63 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 18 years and fulfilled the SLICC classification criteria for SLE. Blood samples were taken from all the SLE patents. 93 cord blood samples obtained from individuals living in Malta were used as a control. DNA extraction was carried out from the blood samples. 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 93.7% of SLE patients were female and they had a mean age of 45.3 years. All the patients were of Caucasian ethnicity. 14.3% had vitamin D deficiency (serum 25-hydroxyvitamin D < 20ng/ml) and 25.4% were vitamin D insufficient (serum 25-hydroxyvitamin D 20-29ng/ml). The results showed that when Apa1 polymorphism was present as a homozygote for the variant allele (AA) 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 Fok1 had an increased prevalence of SLE by around 2 fold (OR = 1.95, CI 1.12-3.38, p = 0.01 and OR = 2.36, CI 1.13-4.91, 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 Fok1 are associated with an increased risk of SLE. Disclosure J. Grech Meli: None. R. Magro: None. J. Debattista: None. N. Aquilina: None. K. Gatt: None. A.A. Borg: None. C. Scerri: None.