Association of the VDR gene with clinical manifestations, complications, and vitamin D status in children with juvenile idiopathic arthritis
Authors:   Research Clinical Institute of Childhood, Moscow, Russian Federation, Loshkova E.V. , Kondratyeva E.I. ,   Research Clinical Institute of Childhood, Moscow, Russian Federation,   Bochkov Research Centre for Medical Genetics, Moscow, Russian Federation, Klimov L.Ya. ,   Stavropol State Medical University, Stavropol, Russian Federation, Podchernyaeva N.S. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Ilyenkova N.A. ,   V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation, Chebysheva S.N. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Shitkovskaya E.P. ,   V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation, Dolbnya S.V. ,   Stavropol State Medical University, Stavropol, Russian Federation, Kuryaninova V.A. ,   Stavropol State Medical University, Stavropol, Russian Federation, Zhekayte E.K. ,   Research Clinical Institute of Childhood, Moscow, Russian Federation,   Bochkov Research Centre for Medical Genetics, Moscow, Russian Federation, Tikhaya M.I. ,   V.F.Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation, Kotova Yu.V. ,   Research Clinical Institute of Childhood, Moscow, Russian Federation, Melyanovskaya Yu.L. ,   Research Clinical Institute of Childhood, Moscow, Russian Federation,   Bochkov Research Centre for Medical Genetics, Moscow, Russian Federation, Erokhina M.I. ,   Research Clinical Institute of Childhood, Moscow, Russian Federation, Khavkin A.I. ,   Research Clinical Institute of Childhood, Moscow, Russian Federation
Published: August 2023

Objective. To conduct an association search between genetic variants (c.1206T>C, c.152T>C, c.1174+283G>A) of the VDR gene and clinical manifestations of juvenile idiopathic arthritis (JIA), need for genetically engineered biological drugs (GEBDs) and vitamin D status in children. Patients and methods. This study included 150 children (mean age: 9.11 ± 2.21 years) with JIA and 333 healthy controls. The determination of serum calcidiol concentrations was performed in all patients. Polymorphic variants of the VDR gene (c.1206T>C, c.1175-9G>T, c.152T>C, c.1174+283G>A) were tested by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technique. Results. Carriers of the minor TT genotype of the genetic variant c.1206T>C(A>G) TaqI are 4 time more likely to develop systemic JIA, 5 time more likely to have high disease activity and uveitis, as well as 9.9 times more often require prescription of GEBDs. Carriers of the minor genotype TT of the genetic variant c.152T>C FokI are 7.7 times more likely to develop systemic JIA and 4.3 times – polyarticular JIA, 6.2 times more likely to have high disease activity and 5.6 times – uveitis, 8 times more often have a severe calcidiol deficiency and 4 times more often require prescription of GEBDs. Carrying the minor AA genotype of the BsmlI polymorphism (c.1174+283G>A) increases the risk of systemic-onset JIA by 17 times, high disease activity and uveitis – by 18 times, and need for GEBDs – by 15 times; carrying the AA and GA genotypes increases the risk of calcidiol deficiency by 5 times and severe calcidiol deficiency by 9 times. Conclusion. All studied genetic variants of the VDR gene verifiably affect the development of clinical manifestations, complications, calcidiol levels and response to therapy in JIA. Key words: VDR gene, juvenile idiopathic arthritis, children, vitamin D, autoimmune disease