AB0015 STUDY OF VDR AND VDBP GENES AS CANDIDATE SUSCEPTIBILITY GENES FOR THE DEVELOPMENT OF IMMUNE-MEDIATED DISEASES IN THE PARAGUAYAN POPULATION
Authors: I. Acosta-Colman, M. Vazquez, S. Cabrera-Villalba, A. Ayala-Lugo, M. E. Acosta, I. Arevalo de Guillen, V. Jolie, M. Duarte, V. Valinotti, R. Contreras, G. Avila, T. Martinez, A. Julià, S. Marsal
Journal: Annals of the Rheumatic Diseases (2021)

Background: Immune Mediated Inflammatory Diseases (IMIDs) are complex diseases that are believed to have a strong interaction between the genome and the environment as part of their aetiology. In studies using the candidate gene strategy, genetic variation in a gene where functionality has been associated with the pathophysiology of the disease under study is being analyzed. In the last decade, polymorphisms of the vitamin D receptor (VDR) and VDBP genes have been more emphatically studied in IMIDs in different populations, but the results reported have not yet been conclusive. Objectives: To identify an association between vitamin D receptor (VDR) and vitamin D-binding protein (VDBP) gene polymorphisms, and IMIDs in Paraguayan patients. Methods: Association study of VDR (SNPs rs731236, rs7975232, rs2228570) and VDBP (rs4588) gene polymorphisms with susceptibility to IMIDs in Paraguayan population. A total of 399 patients with IMIDs (i.e. Systemic Lupus Erythematosus (SLE), Scleroderma (ES), Rheumatoid Arthritis (RA), and Cutaneous Psoriasis (CPS) and 100 hypernormal controls (HC) from the same population were included in this study. Genotyping was performed using Taqman real-time PCR-based technology (Life Technologies, USA). Statistical analysis was performed using Rv3.0.1 statistical language software ( www.R-project.org ). A p value ≤ 0.05 was used for statistical significance. Results: A total of 399 individuals, 100 controls and 299 patients (99 RA, 100 SLE, 50 ES, and 50 PSO) were included. Seventy-six percent were female and 24% were male. The mean age was 43.7±14 years. Four SNPs were genotyped: rs731236, rs7975232, rs2228570, rs4588. The HWE test was not statistically significant for any of the 4 SNPs considered (P&gt;0.05), confirming the quality of genotyping and the absence of technical bias. (Table 1). Table 1. Genotyping of SNPs of the VDR and VDBP gene in Paraguayan population with IMIDs. SNP IMID Minor Allele Major Allele MAF Control MAF Case OR IC.L IC.H p allelic P.Genetic rs731236 SLE G A 0.5 0.4 0.64 0.42 0.97 0.035 0.08 rs731236 RA G A 0.5 0.41 0.69 0.46 1.05 0.071 0.12 rs731236 SS G A 0.5 0.42 0.71 0.42 1.18 0.18 0.37 rs731236 CPS G A 0.5 0.38 0.6 0.36 1.01 0.049 0.042 rs2228570 SLE A G 0.36 0.38 1.14 0.74 1.74 0.6 0.45 rs2228570 RA A G 0.36 0.31 0.83 0.53 1.28 0.4 0.56 rs2228570 SS A G 0.36 0.36 1.02 0.6 1.73 1 0.057 rs2228570 CPS A G 0.36 0.39 1.16 0.68 1.96 0.61 0.83 rs7975232 SLE C A 0.36 0.32 0.82 0.53 1.26 0.4 0.072 rs7975232 RA C A 0.36 0.29 0.72 0.46 1.12 0.14 0.064 rs7975232 SS C A 0.36 0.22 0.49 0.27 0.88 0.012 0.0064 rs7975232 CPS C A 0.36 0.41 1.21 0.72 2.03 0.45 0.016 rs4588 SLE T G 0.23 0.27 1.24 0.77 2 0.42 0.48 rs4588 RA T G 0.23 0.22 0.93 0.56 1.53 0.81 0.84 rs4588 SS T G 0.23 0.21 0.89 0.47 1.65 0.77 0.76 rs4588 CPS T G 0.23 0.29 1.37 0.76 2.43 0.26 0.53 Conclusion: There is evidence of nominal association between VDR SNPs: rs731236 (in SLE and CPS), and rs7975232 (in SS and CPS) and the presence of IMIDs disease in Paraguayan patients. Disclosure of Interests: None declared