Vitamin D receptor gene polymorphism influences lipid profile in patients with juvenile idiopathic arthritis
- 128 Downloads
Vitamin D receptor (VDR) gene FokI (rs2228570) polymorphism was postulated to influence outcome of several inflammatory diseases. The aim of this study was to evaluate the influence of rs2228570 polymorphism on lipid profile and on outcome in patients with juvenile idiopathic arthritis (JIA) treated with etanercept. A total of 153 subjects (62 JIA patients and 91 controls) were screened for the rs2228570 using the PCR-RFLP method. Lipid profile (cholesterol, triacylglycerol, HDL-C, and LDL-C) was determined using standard biochemical analysis in controls, while in JIA patients, it was determined prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA—American College of Rheumatology (ACR) response criteria. There were significant differences in the distribution of genotypes (p = 0.024) and alleles (p = 0.006; OR = 2.222, 95% CI 1.136–4.348) of the rs2228570 between patients and controls. Etanercept treatment significantly increased HDL-C levels (p = 0.006) in JIA patients with FF genotype in comparison to baseline values. No significant differences were seen in JIA—ACR 30/50/70 responses at month 12 between FF and Ff/ff genotype carriers. This is the first study to demonstrate the protective effect of the VDR FokI FF genotype on lipid profile in JIA patients treated with etanercept. However, this has to be confirmed in a larger cohort of patients.
KeywordsEtanercept FokI polymorphism Juvenile idiopathic arthritis Lipid profile
This work was supported by the Ministry of Education, Science, and Technological Development of the Republic of Serbia (grant number III41018).
Compliance with ethical standards
All participants voluntarily agreed to participate in the research, and informed consent was signed by parents or by the patients if they were aged ≥ 12 years. The Ethical Committee of the Medical Faculty in Niš gave consent for conducting this study. All participants were treated in accordance with the Helsinki Declaration. The research was conducted in the Laboratory for Functional Genomics and Proteomics, at the Medical Faculty, University of Niš, Serbia.
Conflict of interests
The authors declare that they have no conflict of interest.
- 1.Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31(2):390–392Google Scholar
- 3.Naranjo A, Sokka T, Descalzo MA, Calvo-Alén J, Hørslev-Petersen K, Luukkainen RK, Combe B, Burmester GR, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Tunc R, Dimic A, Bergman M, Toloza S, Pincus T, QUEST-RA Group (2008) Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res Ther 10(2):R30. https://doi.org/10.1186/ar2383 Google Scholar
- 5.Breda L, Gaspari S, Chiarelli F, Di Marzio D, Nozzi M, Mohn A et al (2013) Relationship between inflammatory markers, oxidant–antioxidant status and intima-media thickness in prepubertal children with juvenile idiopathic arthritis. Clin Res Cardiol 102(1):63–71. https://doi.org/10.1007/s00392-012-0496-3 Google Scholar
- 8.Jurutka PW, Remus LS, Whitfield GK, Thompson PD, Hsieh JC, Zitzer H, Tavakkoli P, Galligan MA, Dang HTL, Haussler CA, Haussler MR (2000) The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB. Mol Endocrinol 14(3):401–420. https://doi.org/10.1210/mend.14.3.0435 Google Scholar
- 13.Ensembl base (2018). Transcript: VDR-201. https://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000111424;r=12:47841537-47943048;t=ENST00000229022. Accessed 14 May 2018
- 14.Karray EF, Ben Dhifallah I, Ben Abdelghani K, Ben Ghorbel I, Khanfir M, Houman H, Hamzaoui K, Zakraoui L (2012) Associations of vitamin D receptor gene polymorphisms FokI and BsmI with susceptibility to rheumatoid arthritis and Behchet’s disease in Tunisians. Joint Bone Spine 79(2):144–148. https://doi.org/10.1016/j.jbspin.2011.06.003 Google Scholar
- 15.Goertz B, Fassbender WJ, Williams JC, Marzeion AM, Bretzel RG, Stracke H, Berliner MN (2003) Vitamin D receptor genotypes are not associated with rheumatoid arthritis or biochemical parameters of bone turnover in German RA patients. Clin Exp Rheumatol 21(3):333–339Google Scholar
- 17.Horneff G, Schulz AC, Klotsche J, Hospach A, Minden K, Foeldvari I, Trauzeddel R, Ganser G, Weller-Heinemann F, Haas JP (2017) Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther 19(1):256. https://doi.org/10.1186/s13075-017-1462-2 Google Scholar
- 18.Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A (1997) Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 40:1202–1209Google Scholar
- 19.Pani MA, Knapp M, Donner H, Braun J, Baur MP, Usadel KH, Badenhoop K (2000) Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans. Diabetes 49(3):504–507Google Scholar
- 20.Masi L, Cimaz R, Simonini G, Bindi G, Stagi S, Gozzini A, Malentacchi C, Brandi ML, Falcini F (2002) Association of low bone mass with vitamin D receptor gene and calcitonin receptor gene polymorphisms in juvenile idiopathic arthritis. J Rheumatol 29(10):2225–2231Google Scholar
- 22.Williams C, Hayman L, Daniels S, Robinson T, Steinberger J, Paridon S, Bazzarre T (2002) Cardiovascular health in childhood: a statement for health professionals from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 106(1):143–160Google Scholar
- 23.van Eijk I, de Vries M, Levels J, Peters M, Huizer E, Dijkmans B et al (2009) Improvement of lipid profile is accompanied by atheroprotective alterations in high-density lipoprotein composition upon tumor necrosis factor blockade: a prospective cohort study in ankylosing spondylitis. Arthritis Rheum 60(5):1324–1330. https://doi.org/10.1002/art.24492 Google Scholar
- 24.Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M, Sibilia J, Koné-Paut I, Gandon-Laloum S, LeBideau M, Bader-Meunier B, Mouy R, Debré M, Landais P, Prieur AM (2003) Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 48(4):1093–1101. https://doi.org/10.1002/art.10885 Google Scholar
- 34.Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K et al (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12(6):915–992Google Scholar
- 35.Alexeeva EI, Namazova-Baranova LS, Bzarova TM, Valieva SI, Denisova RV, Sleptsova TV, Isaeva KB, Chomahidze AM, Taibulatov NI, Fetisova AN, Karaseva AV, Baranov AA (2017) Predictors of the response to etanercept in patients with juvenile idiopathic arthritis without systemic manifestations within 12 months: results of an open-label, prospective study conducted at the National Scientific and Practical Center of Children’s Health, Russia. Pediatr Rheumatol Online J 15(1):51. https://doi.org/10.1186/s12969-017-0178-9 Google Scholar
- 37.Basic J, Pavlovic D, Jevtovic-Stoimenov T, Vojinovic J, Susic G, Stojanovic I, Kocic G, Milosevic V, Cvetkovic T, Marinkovic M, Veljkovic A (2010) Etanercept reduces matrix metalloproteinase-9 level in children with polyarticular juvenile idiopathic arthritis and TNF-α-308GG genotype. J Physiol Biochem 66(2):173–180. https://doi.org/10.1007/s13105-010-0022-x Google Scholar
- 38.Jevtovic Stoimenov T, Despotovic M, Stojanovic S, Basic J, Pavlovic D (2017) Polymorphic variants of antioxidative defense enzymes and their gene-gene epistatic interactions in systemic lupus erythematode patients. Clin Rheumatol 36(9):2019–2026. https://doi.org/10.1007/s10067-017-3755-x Google Scholar