FGF-23, Klotho and Vitamin D Levels in Scleroderma
-
Ravan AHMADI
,
Mehrzad HAJIALILO
,
Amir GHORBANIHAGHJO
,
Ali MOTA
,
Sina RAEISI
,
Nasrin BARGAHI
,
Mohammad VALILO
,
Farahnaz ASKARIAN
Abstract
Background: Scleroderma is a chronic connective tissue disease of unknown etiology. Vitamin D and parathyroid hormone (PTH) that play particular functions in calcium and phosphate homeostasis may be involved in the etiology of this disorder. Klotho, the co-receptor of the fibroblast growth factor 23 (FGF-23), can interfere with calcium and phosphate metabolism. The purpose of this study was to evaluate serum Klotho, FGF-23, intact PTH (iPTH) and vitamin D levels in scleroderma patients compared with the healthy controls.
Methods: The study was performed in Biotechnology Research Center, Tabriz University of Medical Sciences (TUMS) from 2014-2015. Sixty scleroderma patients based on the classification criteria of systemic sclerosis and 30 age- and sex-matched healthy controls were included in this study. Serum Klotho, FGF-23, 25-hydroxy vitamin D (25-OH Vit D), and iPTH levels were analyzed using ELISA.
Results: Serum levels of Klotho and 25-OH Vit D in the scleroderma patients were lower than those in the healthy controls (P˂0.001). In addition, scleroderma patients had higher serum iPTH levels than the controls (P<0.001). There was no significant difference in serum FGF-23 levels between the patients and controls (P=0.202).
Conclusion: The decreased serum Klotho, 25-OH Vit D, and increased iPTH levels in the scleroderma patients may be associated with the pathogenesis of this disease and could be considered a future therapeutic target.
David M (1981). A Case of Sclerodermia Mentioned by Hippocrates in His Aphorisms. Korot, 8:61-63.
Chifflot H, Fautrel B, Sordet C, Chatelus E, Sibilia J (2008). Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin Arthritis Rheum, 37: 223-235.
Arnson Y, Amital H, Agmon-Levin N, et al (2011). Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev, 10:490-494.
Mayes MD, Bossini-Castillo L, Gorlova O, et al (2014). Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis. Am J Hum Genet, 94:47-61.
Marie I, Gehanno J-F, Bubenheim M, et al (2014). Prospective study to evaluate the association between systemic sclerosis and occupational exposure and review of the literature. Autoimmun Rev, 13:151-156.
Arnson Y, Amital H, Shoenfeld Y (2007). Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis, 66:1137-1142.
Caramaschi P, Dalla Gassa A, Ruzzenente O, Volpe A, Ravagnani V, Tinazzi I, Barausse G, Bambara LM, Biasi D (2010). Very low levels of vitamin D in systemic sclerosis patients. Clin Rheumatol, 29:1419-1425.
Hu MC, Shi M, Zhang J, Pastor J, et al (2010). Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J, 24:3438-3450.
Fructuoso AIS, Maestro ML, Pérez-Flores I, et al (2012). Serum level of fibroblast growth factor 23 in maintenance renal transplant patients. Nephrol Dial Transplant, 27:4227-4235.
Uzum AK, Salman S, Telci A, Boztepe H, Tanakol R, Alagol F, Ozbey NC (2010). Effects of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women in short term. Eur J Endocrinol, 163:825-831.
Melov S, Rosen CJ (2016). Aging and the Bone-Muscle Interface. In:Advances in Geroscience. Ed(s): Springer, pp. 257-275.
Hoogen F, Khanna D, Fransen J, et al (2013). 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis, 72:1747-55.
Medsger Jr T, Silman A, Steen V, et al (1999). A disease severity scale for systemic sclerosis: development and testing. J Rheumatol, 26:2159-2167.
Wu M, Assassi S (2013). The role of type 1 interferon in systemic sclerosis. Front Immunol, 6;4:266.
Tizaoui K, Kaabachi W, Hamzaoui A, Hamzaoui K (2015). Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case–control studies. Cell Mol Immunol, 12:243-252.
Lee YH, Bae S-C, Choi SJ, Ji JD, Song GG (2011). Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep, 38:3643-3651.
Maalej A, Petit-Teixeira E, Michou L, Rebai A, Cornelis F, Ayadi H (2005). Association study of VDR gene with rheumatoid arthritis in the French population. Genes Immun, 6:707-711.
Carvalho C, Marinho A, Leal B, et al (2015). Association between vitamin D receptor (VDR) gene polymorphisms and systemic lupus erythematosus in Portuguese patients. Lupus, 24:846-53
Calzolari G, Data V, Carignola R, Angeli A (2009). Hypovitaminosis D in systemic sclerosis. J Rheumatol, 36:2844.
Horger M, Fierlbeck G, Kuemmerle-Deschner J, Tzaribachev N, Wehrmann M, Claussen CD, Fritz J (2008). MRI findings in deep and generalized morphea (localized scleroderma). Am J Roentgenol, 190:32-39.
Kuro-o M (2012). Klotho in health and disease. Curr Opin Nephrol Hypertens, 21:362-368.
Avouac J, Walker U, Tyndall A, et al (2010). Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database. J Rheumatol ,37:1488-501.
Hasegawa M, Fujimoto M, Kikuchi K, Takehara K (1997). Elevated serum levels of interleukin 4 (IL-4), IL-10, and IL-13 in patients with systemic sclerosis. J Rheumatol, 24:328-332.
Moreno JA, Izquierdo MC, Sanchez-Niño MD et al (2011). The inflammatory cytokines TWEAK and TNFα reduce renal klotho expression through NFκB. J Am Soc Nephrol, 22:1315-1325.
Wu X, Ge H, Gupte J, Weiszmann J, Shimamoto G, Stevens J, Hawkins N, Lemon B, Shen W, Xu J (2007). Co-receptor requirements for fibroblast growth factor-19 signaling. J Biol Chem, 282:29069-29072.
Wu X, Lemon B, Li X, Gupte J, Weiszmann J, Stevens J, Hawkins N, Shen W, Lindberg R, Chen J-L (2008). C-terminal tail of FGF19 determines its specificity toward Klotho co-receptors. J Biol Chem, 283:33304-33309.
Martin A, David V, Quarles LD (2012). Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev, 92:131-155.
de Borst MH, Vervloet MG, ter Wee PM, Navis G (2011). Cross talk between the renin-angiotensin-aldosterone system and vitamin D-FGF-23-klotho in chronic kidney disease. J Am Soc Nephrol, 22:1603-1609.
Shenavandeh S, Radmanesh S, Sarvestani EK, Nazarinia M, Omrani GR (2015). Fibroblast growth factor-23 in patients with systemic sclerosis: A case–control study. The Egyptian Rheumatologist, 38(2):105-109.
Levin A, Bakris G, Molitch M, Smulders M, Tian J, Williams L, Andress D (2007). Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int, 71:31-38.
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| Issue | Vol 46 No 4 (2017) | |
| Section | Original Article(s) | |
| Keywords | ||
| FGF-23 Klotho Scleroderma 25-hydroxy vitamin D | ||
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