AB0976 Association of Vitamin D Receptor Polymorphisms with Juvenile Idiopathic Arthritis (JIA)
Authors: F. Falcini, F. Marini, S. Stagi, G. Lepri, D. Rigante, M. Matucci-Cerinic, M.L. Brandi
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> JIA is the most common chronic arthritis of childhood. Vitamin D is a potential immuno-modulator in many conditions, including autoimmune diseases. Its influence in JIA is still unclear. Specific polymorphisms of vitamin D receptor gene (<i>VDR</i>) have recently been associated with different biologic responses to vitamin D itself. <h3>Objectives</h3> 90 Italian children, adolescents and young adults with poli- or oligoarticular onset of JIA were studied. <i>VDR</i> polymorphisms were analysed by PCR-based sequencing (<i>CDX2</i> in the promoter region) and PCR-based enzymatic digestions (<i>FokI</i> in exon 2, <i>BsmI</i> and <i>ApaI</i> in intron 8, and <i>TaqI</i> in exon 9) in the genomic DNA from blood of patients. 2221 healthy Italian unrelated individuals have been used as controls for <i>VDR</i> polymorphism frequencies. Distribution of <i>VDR</i> polymorphisms has been evaluated in patients <i>vs</i> controls, in patients with active and inactive disease, and in patients with poli- or oligoarticular JIA. <h3>Methods</h3> The distribution of <i>FokI</i>, <i>BsmI</i>, and <i>TaqI</i> polymorphisms did not show any significant difference between subjects with JIA and controls. Conversely, significant statistical differences in the distribution of <i>CDX2</i> and <i>ApaI</i> genotypes were found, respectively with the <i>CDX2</i> GG genotype (Yates-corrected chi-square 6.56; Odds ratio=1.80; <i>p</i>=0.0104) and the TT <i>ApaI</i> genotype (Yates-corrected chi-square 20.97; Odds ratio=2.67; <i>p</i>=0.0000), both more frequent in JIA than in controls. Also the G allele of <i>CDX2</i> (Yates-corrected chi-square 6.12; Odds ratio=1.60; <i>p</i>=0.0134) and the T allele of <i>ApaI</i> (Yates-corrected chi-square 19.69; Odds ratio=2.05; <i>p</i>=0.0000) was more frequent in JIA. No statistical differences were found for all the analysed <i>VDR</i> polymorphisms, between the poliarticular <i>vs</i> oligoarticular forms. No significant association was found between <i>VDR</i> polymorphisms and active or inactive forms of JIA, neither with osteopenic or normal bone mineral density status. <h3>Conclusions</h3> Pathogenetic mechanisms influencing the predisposition to JIA are poorly elucidated and autoimmune dysfunctions are strongly suspected. This genetic study found a significantly higher frequency of the GG genotype of <i>VDR</i><i>CDX2</i> polymorphism and TT genotype of <i>VDR</i><i>ApaI</i> polymorphism in patients with JIA. The <i>CDX2</i> polymorphism is located in the promoter region of the <i>VDR</i> gene and has been associated with <i>VDR</i> mRNA expression, while the ApaI polymorphism has been associated with the stability of <i>VDR</i> mRNA. Therefore, we can speculate that <i>CDX2</i> GG genotype and <i>ApaI</i> TT genotype can both influence the expression of the VDR protein, presumably resulting in a reduced receptor activity with subsequent decreased response to vitamin D and potential immunity deregulation, favouring the development of JIA. Conversely, <i>VDR</i> polymorphisms seem not to have any influence for patients9 active or non-active status, both for the oligoarticular and poliarticular form of the disease. <h3>Disclosure of Interest</h3> None declared