Study of Vitamin D Status and Vitamin D Receptor Polymorphisms in a Cohort of Italian Patients with Juvenile Idiopathic Arthritis

Overview

Journal Sci Rep

Specialty Science

Date 2020 Oct 17

PMID 33067526

Citations 12

Authors

Francesca Marini

Fernanda Falcini

Stefano Stagi

Sergio Fabbri

Simone Ciuffi

Donato Rigante

Marco Matucci Cerinic

Maria Luisa Brandi

Affiliations

Soon will be listed here.

Abstract

Juvenile idiopathic arthritis (JIA) is the most common chronic arthritis of children and adolescents. Autoimmune mechanisms are suspected to have a central role in its development. Vitamin D is an immuno-modulator in a variety of conditions, including autoimmune diseases. Low levels of vitamin D have commonly been found in JIA patients, but the influence of this hormone insufficiency in JIA pathogenesis is still unclear. Vitamin D receptor (VDR) mediates a great majority of vitamin D biological activities; specific polymorphisms of the VDR gene have been associated with different biologic responses to vitamin D. In this study, we analysed clinical characteristics of a cohort of 103 Italian JIA patients. The distribution of VDR polymorphisms in affected patients versus healthy controls was evaluated, as well as if and how these polymorphic variants associate with different disease presentations (active disease vs non-active disease), different JIA subtypes, serum levels of 25-hydroxy-vitamin D and parathyroid hormone (PTH), and lumbar spine Z-score values (osteopenia vs normal bone mineral density). A great majority of our JIA patients (84.5%) showed a suboptimal vitamin D status, in many cases (84.1%) not solved by vitamin D supplementation. Vitamin D status resulted to be independent of VDR genotypes. ApaI genotypes showed a highly significant different distribution between JIA patients and unaffected controls, with both the TT genotype and the T allele significantly more frequent in patient group.

Citing Articles

The impact of genetic variants related to vitamin D and autoimmunity: A systematic review.

Trefilio L, Bottino L, de Carvalho Cardoso R, Montes G, Fontes-Dantas F Heliyon. 2024; 10(7):e27700.

PMID: 38689997 PMC: 11059421. DOI: 10.1016/j.heliyon.2024.e27700.

Seasonal and Treatment-Related Variation in 25-Hydroxy Vitamin D Concentration in Patients with Rheumatoid Arthritis.

Cieslewicz A, Korzeniowska K, Grabanska-Martynska K, Jablecka A, Hrycaj P J Clin Med. 2024; 13(4).

PMID: 38398286 PMC: 10889237. DOI: 10.3390/jcm13040973.

The rs11568820 Variant in the Promoter Region of Vitamin D Receptor Gene Is Associated with Clinical Remission in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors.

Latini A, De Benedittis G, Conigliaro P, Bonini C, Morgante C, Iacovantuono M Genes (Basel). 2024; 15(2).

PMID: 38397223 PMC: 10887840. DOI: 10.3390/genes15020234.

Can vitamin D be an adjuvant therapy for juvenile rheumatic diseases?.

Stawicki M, Abramowicz P, Sokolowska G, Wolejszo S, Grant W, Konstantynowicz J Rheumatol Int. 2023; 43(11):1993-2009.

PMID: 37566255 PMC: 10495493. DOI: 10.1007/s00296-023-05411-5.

Nutritional Aspects of Juvenile Idiopathic Arthritis: An A to Z for Dietitians.

Grammatikopoulou M, Gkiouras K, Syrmou V, Vassilakou T, Simopoulou T, Katsiari C Children (Basel). 2023; 10(2).

PMID: 36832332 PMC: 9955348. DOI: 10.3390/children10020203.

References

Slominski A, Kim T, Hobrath J, Janjetovic Z, Oak A, Postlethwaite A . Characterization of a new pathway that activates lumisterol in vivo to biologically active hydroxylumisterols. Sci Rep. 2017; 7(1):11434. PMC: 5595834. DOI: 10.1038/s41598-017-10202-7. View

Slominski A, Kim T, Li W, Postlethwaite A, Tieu E, Tang E . Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland. Sci Rep. 2015; 5:14875. PMC: 4597207. DOI: 10.1038/srep14875. View

Slominski A, Kim T, Shehabi H, Semak I, Tang E, Nguyen M . In vivo evidence for a novel pathway of vitamin D₃ metabolism initiated by P450scc and modified by CYP27B1. FASEB J. 2012; 26(9):3901-15. PMC: 3425822. DOI: 10.1096/fj.12-208975. View

Kostik M, Smirnov A, Demin G, Scheplyagina L, Larionova V . Juvenile idiopathic arthritis patients and their skeletal status: possible role of vitamin D receptor gene polymorphism. Mol Biol Rep. 2014; 41(4):1937-43. DOI: 10.1007/s11033-014-3040-x. View

Reed A, Haugen M, Pachman L, Langman C . 25-Hydroxyvitamin D therapy in children with active juvenile rheumatoid arthritis: short-term effects on serum osteocalcin levels and bone mineral density. J Pediatr. 1991; 119(4):657-60. DOI: 10.1016/s0022-3476(05)82424-2. View

Weiss J, Ilowite N . Juvenile idiopathic arthritis. Pediatr Clin North Am. 2005; 52(2):413-42, vi. DOI: 10.1016/j.pcl.2005.01.007. View

Stagi S, Bertini F, Cavalli L, Matucci-Cerinic M, Brandi M, Falcini F . Determinants of vitamin D levels in children, adolescents, and young adults with juvenile idiopathic arthritis. J Rheumatol. 2014; 41(9):1884-92. DOI: 10.3899/jrheum.131421. View

Masi L, Cimaz R, Simonini G, Bindi G, Stagi S, Gozzini A . Association of low bone mass with vitamin d receptor gene and calcitonin receptor gene polymorphisms in juvenile idiopathic arthritis. J Rheumatol. 2002; 29(10):2225-31. View

Adorini L, Penna G . Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol. 2008; 4(8):404-12. DOI: 10.1038/ncprheum0855. View

10.

Li Q, Verma I . NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002; 2(10):725-34. DOI: 10.1038/nri910. View

11.

Hypponen E, Laara E, Reunanen A, Jarvelin M, Virtanen S . Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001; 358(9292):1500-3. DOI: 10.1016/S0140-6736(01)06580-1. View

12.

Ruiz-Irastorza G, Egurbide M, Olivares N, Martinez-Berriotxoa A, Aguirre C . Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford). 2008; 47(6):920-3. DOI: 10.1093/rheumatology/ken121. View

13.

Basic J, Vojinovic J, Jevtovic-Stoimenov T, Despotovic M, Susic G, Lazarevic D . Vitamin D receptor gene polymorphism influences lipid profile in patients with juvenile idiopathic arthritis. Clin Rheumatol. 2018; 38(1):117-124. DOI: 10.1007/s10067-018-4264-2. View

14.

Finch S, Rosenberg A, Vatanparast H . Vitamin D and juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2018; 16(1):34. PMC: 5956785. DOI: 10.1186/s12969-018-0250-0. View

15.

Yang C, Leung P, Adamopoulos I, Gershwin M . The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013; 45(2):217-26. PMC: 6047889. DOI: 10.1007/s12016-013-8361-3. View

16.

Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C . Vitamin D: modulator of the immune system. Curr Opin Pharmacol. 2010; 10(4):482-96. DOI: 10.1016/j.coph.2010.04.001. View

17.

Manios Y, Moschonis G, Lambrinou C, Tsoutsoulopoulou K, Binou P, Karachaliou A . A systematic review of vitamin D status in southern European countries. Eur J Nutr. 2017; 57(6):2001-2036. DOI: 10.1007/s00394-017-1564-2. View

18.

van Etten E, Verlinden L, Giulietti A, Ramos-Lopez E, Branisteanu D, Ferreira G . The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol. 2007; 37(2):395-405. DOI: 10.1002/eji.200636043. View

19.

Cutolo M, Pizzorni C, Sulli A . Vitamin D endocrine system involvement in autoimmune rheumatic diseases. Autoimmun Rev. 2011; 11(2):84-7. DOI: 10.1016/j.autrev.2011.08.003. View

20.

Agmon-Levin N, Mosca M, Petri M, Shoenfeld Y . Systemic lupus erythematosus one disease or many?. Autoimmun Rev. 2011; 11(8):593-5. DOI: 10.1016/j.autrev.2011.10.020. View