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16.06.2020 | Original Article

Associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in systemic lupus erythematosus patients

verfasst von: Qiu-Yue Lou, Zhen Li, Ying Teng, Qiao-Mei Xie, Man Zhang, Shun-Wei Huang, Wen-Fei Li, Yang-Fan Chen, Fa-Ming Pan, Sheng-Qian Xu, Jing Cai, Shuang Liu, Jin-Hui Tao, Sheng-Xiu Liu, Hai-Liang Huang, Fang Wang, Hai-Feng Pan, Hong Su, Zhi-Wei Xu, Wen-Biao Hu, Yan-Feng Zou

Erschienen in: Clinical Rheumatology | Ausgabe 1/2021

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Abstract

Objectives

To explore the associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid (GC) efficacy, anxiety, depression, and health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE) patients.

Methods

All subjects were collected from the First and the Second Affiliated Hospital of Anhui Medical University in Hefei, China, during 2011 to 2015. In the case–control study, 541 SLE patients and 543 controls were recruited. In the follow-up study, 466 patients completed the 12-week follow-up and then were divided into GC-sensitive and GC-insensitive groups. Genotyping was determined using Multiplex SNaPshot technique. Data were analyzed using chi-square test and univariate and multivariate logistic regression analyses.

Results

rs4713904, rs9368878, and rs7757037 of FKBP5 were associated with depression in SLE patients (rs4713904, P_BH = 0.037; rs9368878, P_BH = 0.001; rs7757037, P_BH = 0.003). Moreover, rs4713904 was associated with GC efficacy in males with SLE (P_BH = 0.011). The rs755658 of FKBP5 was associated with improvement in social function (P_BH = 0.022) and mental component summary (P_BH = 0.028). The rs4713907 of FKBP5 was related to improvement in total score of SF-36, bodily pain, and mental component summary score (all P_BH = 0.018). Furthermore, the rs12582595 of FKBP4 was correlated with general health improvement (P_BH = 0.033). No associations were seen between FKBP4/FKBP5 gene polymorphisms and SLE susceptibility and anxiety.

Conclusions

FKBP5 gene polymorphisms may be associated with depression and GC efficacy of SLE patients. Meanwhile, the genetic polymorphisms of FKBP4 and FKBP5 genes may be associated with HRQOL improvement in SLE patients.

Key Points

• FKBP5 gene polymorphisms were associated with depression of SLE patients.

• FKBP5 gene polymorphisms were associated with GC efficacy of SLE patients.

• FKBP5 gene polymorphisms were associated with HRQOL improvement in SLE patients.

• FKBP4 gene polymorphisms were associated with HRQOL improvement in SLE patients.

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Mohan C, Putterman C (2015) Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis. Nat Rev Nephrol 11(6):329–341. https://doi.org/10.1038/nrneph.2015.33CrossRefPubMed

Do SC, Druzin ML (2019) Systemic lupus erythematosus in pregnancy: high risk, high reward. Curr Opin Obstet Gynecol 31(2):120–126. https://doi.org/10.1097/GCO.0000000000000528CrossRefPubMed

Cui Y, Sheng Y, Zhang X (2013) Genetic susceptibility to SLE: recent progress from GWAS. J Autoimmun 41:25–33. https://doi.org/10.1016/j.jaut.2013.01.008CrossRefPubMed

Zgajnar NR, De Leo SA, Lotufo CM, Erlejman AG, Piwien-Pilipuk G, Galigniana MD (2019) Biological actions of the Hsp90-binding immunophilins FKBP51 and FKBP52. Biomolecules 9(2):52. https://doi.org/10.3390/biom9020052CrossRefPubMedCentral

Storer CL, Dickey CA, Galigniana MD, Rein T, Cox MB (2011) FKBP51 and FKBP52 in signaling and disease. Trends Endocrinol Metab 22(12):481–490. https://doi.org/10.1016/j.tem.2011.08.001CrossRefPubMedPubMedCentral

Barcellos LF, May SL, Ramsay PP, Quach HL, Lane JA, Nititham J, Noble JA, Taylor KE, Quach DL, Chung SA, Kelly JA, Moser KL, Behrens TW, Seldin MF, Thomson G, Harley JB, Gaffney PM, Criswell LA (2009) High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions. PLoS Genet 5(10):e1000696. https://doi.org/10.1371/journal.pgen.1000696CrossRefPubMedPubMedCentral

Slager SL, Skibola CF, Di Bernardo MC, Conde L, Broderick P, McDonnell SK, Goldin LR, Croft N, Holroyd A, Harris S et al (2012) Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia. Blood 120(4):843–846. https://doi.org/10.1182/blood-2012-03-413591CrossRefPubMedPubMedCentral

Little J, Parker B, Lunt M, Hanly JG, Urowitz MB, Clarke AE, Romero-Diaz J, Gordon C, Bae S-C, Bernatsky S, Wallace DJ, Merrill JT, Buyon J, Isenberg DA, Rahman A, Ginzler EM, Petri M, Dooley MA, Fortin P, Gladman DD, Steinsson K, Ramsey-Goldman R, Khamashta MA, Aranow C, Mackay M, Alarcón GS, Manzi S, Nived O, Jönsen A, Zoma AA, van Vollenhoven RF, Ramos-Casals M, Ruiz-Irastorza G, Sam Lim S, Kalunian KC, Inanc M, Kamen DL, Peschken CA, Jacobsen S, Askanase A, Sanchez-Guerrero J, Bruce IN (2018) Glucocorticoid use and factors associated with variability in this use in the Systemic Lupus International Collaborating Clinics inception cohort. Rheumatology (Oxford) 57(4):677–687. https://doi.org/10.1093/rheumatology/kex444CrossRef

Felten R, Sagez F, Gavand PE, Martin T, Korganow AS, Sordet C, Javier RM, Soulas-Sprauel P, Rivière M, Scher F, Poindron V, Guffroy A, Arnaud L (2019) 10 most important contemporary challenges in the management of SLE. Lupus Sci Med 6(1):e000303. https://doi.org/10.1136/lupus-2018-000303CrossRefPubMedPubMedCentral

10.

Mosca M, Tani C, Carli L, Bombardieri S (2011) Glucocorticoids in systemic lupus erythematosus. Clin Exp Rheumatol 29:S126–S129PubMed

11.

Melo AK, Melo MR, Saramago AB, Demartino G, Souza BD, Longui CA (2013) Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission. Genet Mol Res 12(2):2010–2019. https://doi.org/10.4238/2013.February.19.1CrossRefPubMed

12.

Merkulov VM, Merkulova TI, Bondar NP (2017) Mechanisms of brain glucocorticoid resistance in stress-induced psychopathologies. Biochemistry (Mosc) 82(3):351–365. https://doi.org/10.1134/S0006297917030142CrossRef

13.

Bai R, Liu S, Zhao Y, Cheng Y, Li S, Lai A, Xie Z, Xu X, Lu Z, Xu J (2016) Depressive and anxiety disorders in systemic lupus erythematosus patients without major neuropsychiatric manifestations. J Immunol Res 2016:2829018–2829017. https://doi.org/10.1155/2016/2829018CrossRefPubMedPubMedCentral

14.

Yilmaz-Oner S, Oner C, Dogukan FM, Moses TF, Demir K, Tekayev NYilmaz N, Tuglular S, Direskeneli H (2015) Anxiety and depression predict quality of life in Turkish patients with systemic lupus erythematosus. Clin Exp Rheumatol 33(3):360–365PubMed

15.

Scheimann JR, Mahbod P, Morano R, Frantz L, Packard B, Campbell KHerman JP (2018) Deletion of glucocorticoid receptors in forebrain GABAergic neurons alters acute stress responding and passive avoidance behavior in female mice. Front Behav Neurosci 12:325. https://doi.org/10.3389/fnbeh.2018.00325CrossRefPubMedPubMedCentral

16.

Criado-Marrero M, Rein T, Binder EB, Porter JT, Koren J 3rd, Blair LJ (2018) Hsp90 and FKBP51: complex regulators of psychiatric diseases. Philos Trans R Soc Lond Ser B Biol Sci 373(1738):20160532. https://doi.org/10.1098/rstb.2016.0532CrossRef

17.

Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Pütz B, Papiol S, Seaman S, Lucae S, Kohli MA, Nickel T, Künzel HE, Fuchs B, Majer M, Pfennig A, Kern N, Brunner J, Modell S, Baghai T, Deiml T, Zill P, Bondy B, Rupprecht R, Messer T, Köhnlein O, Dabitz H, Brückl T, Müller N, Pfister H, Lieb R, Mueller JC, Lõhmussaar E, Strom TM, Bettecken T, Meitinger T, Uhr M, Rein T, Holsboer F, Muller-Myhsok B (2004) Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 36(12):1319–1325. https://doi.org/10.1038/ng1479CrossRefPubMed

18.

Zou YF, Xu JH, Pan FM, Tao JH, Xu SQ, Xiao H, Liu S, Cai J, LianL CPL et al (2015) Glucocorticoid receptor genetic polymorphisms is associated with improvement of health-related quality of life in Chinese population with systemic lupus erythematosus. Clin Rheumatol 34(9):1537–1544. https://doi.org/10.1007/s10067-015-3027-6CrossRefPubMed

19.

Pan S, Liu ZW, Shi S, Ma X, Song WQ, Guan GC, Zhang Y, Zhu SM, Liu FQ, Liu B, Tang ZG, Wang JK, Lv Y (2017) Hamilton rating scale for depression-24 (HAM-D(24)) as a novel predictor for diabetic microvascular complications in type 2 diabetes mellitus patients. Psychiatry Res 258:177–183. https://doi.org/10.1016/j.psychres.2017.07.050CrossRefPubMed

20.

Zhao J, Long X, Yang Y, Pan H, Zhang L, Guo Z, Wang J, Lan J (2019) Identification and characterization of a pig FKBP5 gene with a novel expression pattern in lymphocytes and granulocytes. Anim Biotechnol 30(4):302–310. https://doi.org/10.1080/10495398.2018.1487305CrossRefPubMed

21.

Matsushita R, Hashimoto A, Tomita T, Yoshitawa H, Tanaka S, Endo H, Hirohata S (2010) Enhanced expression of mRNA for FK506-binding protein 5 in bone marrow CD34 positive cells in patients with rheumatoid arthritis. Clin Exp Rheumatol 28(1):87–90PubMed

22.

Reynolds PD, Ruan Y, Smith DF, Scammell JG (1999) Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51. J Clin Endocrinol Metab 84(2):663–669. https://doi.org/10.1210/jcem.84.2.5429CrossRefPubMed

23.

Maltese P, Palma L, Sfara C, de Rocco P, Latiano A, Palmieri O, Corritore G, Annese V, Magnani M (2012) Glucocorticoid resistance in Crohn's disease and ulcerative colitis: an association study investigating GR and FKBP5 gene polymorphisms. Pharm J 12(5):432–438. https://doi.org/10.1038/tpj.2011.26CrossRef

24.

Krasselt M, Baerwald C (2019) Sex, symptom severity, and quality of life in rheumatology. Clin Rev Allergy Immunol 56(3):346–361. https://doi.org/10.1007/s12016-017-8631-6CrossRefPubMed

25.

Tozzi L, Farrell C, Booij L, Doolin K, Nemoda Z, Szyf M, Pomares FB, Chiarella J, O'Keane V, Frodl T (2018) Epigenetic changes of FKBP5 as a link connecting genetic and environmental risk factors with structural and functional brain changes in major depression. Neuropsychopharmacology 43(5):1138–1145. https://doi.org/10.1038/npp.2017.290CrossRefPubMed

26.

Parade SH, Parent J, Rabemananjara K, Seifer R, Marsit CJ, Yang BZ, Zhang H, Tyrka AR (2017) Change in FK506 binding protein 5 (FKBP5) methylation over time among preschoolers with adversity. Dev Psychopathol 29(5):1627–1634. https://doi.org/10.1017/S0954579417001286CrossRefPubMedPubMedCentral

27.

Shinozaki G, Jowsey S, Amer H, Biernacka J, Colby C, Walker D, Black J, Rundell J, Stegall M, Mrazek DA (2011) Relationship between FKBP5 polymorphisms and depression symptoms among kidney transplant recipients. Depress Anxiety 28(12):1111–1118. https://doi.org/10.1002/da.20879CrossRefPubMed

28.

Xu J, Wang R, Liu Y, Liu D, Jiang H, Pan F (2017) FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats. J Psychiatr Res 95:102–113. https://doi.org/10.1016/j.jpsychires.2017.08.010CrossRefPubMed

29.

Resmini E, Santos A, Aulinas A, Webb SM, Vives-Gilabert Y, Cox O, Wand G, Lee RS (2016) Reduced DNA methylation of FKBP5 in Cushing's syndrome. Endocrine 54(3):768–777. https://doi.org/10.1007/s12020-016-1083-6CrossRefPubMedPubMedCentral

30.

Tatro ET, Nguyen TB, Bousman CA, Masliah E, Grant I, Atkinson JH, Everall IP (2010) Correlation of major depressive disorder symptoms with FKBP5 but not FKBP4 expression in human immunodeficiency virus-infected individuals. J Neuro-Oncol 16(5):399–404. https://doi.org/10.3109/13550284.2010.504248CrossRef

31.

Hirakawa H, Akiyoshi J, Muronaga M, Tanaka Y, Ishitobi Y, Inoue A, Oshita H, Aizawa S, Masuda K, Higuma H, Kanehisa M, Ninomiya T, Kawano Y (2016) FKBP5 is associated with amygdala volume in the human brain and mood state: a voxel-based morphometry (VBM) study. Int J Psychiatry Clin Pract 20(2):106–115. https://doi.org/10.3109/13651501.2016.1144772CrossRefPubMed

32.

Roberts S, Keers R, Breen G, Coleman JRI, Jöhren P, Kepa A, Lester KJ, Margraf J, Scheider S, Teismann T, Wannemüller A, Eley TC, Wong CCY (2019) DNA methylation of FKBP5 and response to exposure-based psychological therapy. Am J Med Genet B Neuropsychiatr Genet 180:150–158. https://doi.org/10.1002/ajmg.b.32650CrossRefPubMed

33.

Touma C, Gassen NC, Herrmann L, Cheung-Flynn J, Büll DR, Ionescu IA, Heinzmann JM, Knapman A, Siebertz A, Depping AM, Hartmann J, Hausch F, Schmidt MV, Holsboer F, Ising M, Cox MB, Schmidt U, Rein T (2011) FK506 binding protein 5 shapes stress responsiveness: modulation of neuroendocrine reactivity and coping behavior. Biol Psychiatry 70(10):928–936. https://doi.org/10.1016/j.biopsych.2011.07.023CrossRefPubMed

34.

Attwood BK, Bourgognon J-M, Patel S, Mucha M, Schiavon E, Skrzypiec AE, Young KW, Shiosaka S, Korostynski M, Piechota M, Przewlocki R, Pawlak R (2011) Neuropsin cleaves EphB2 in the amygdala to control anxiety. Nature 473(7347):372–375. https://doi.org/10.1038/nature09938CrossRefPubMedPubMedCentral

35.

Hartmann J, Wagner KV, Gaali S, Kirschner A, Kozany C, Rühter G, Dedic N, Häusl AS, Hoeijmakers L, Westerholz S et al (2015) Pharmacological inhibition of the psychiatric risk factor FKBP51 has anxiolytic properties. J Neurosci 35(24):9007–9016. https://doi.org/10.1523/JNEUROSCI.4024-14.2015CrossRefPubMedPubMedCentral

36.

Hartmann J, Wagner KV, Dedic N, Marinescu D, Scharf SH, Wang XD, Deussing JM, Hausch F, Rein T, Schmidt U, Holsboer F, Müller MB, Schmidt MV (2012) Fkbp52 heterozygosity alters behavioral, endocrine and neurogenetic parameters under basal and chronic stress conditions in mice. Psychoneuroendocrinology 37(12):2009–2021. https://doi.org/10.1016/j.psyneuen.2012.04.017CrossRefPubMed

37.

Young MJ, Geiszler PC, Pardon MC (2016) A novel role for the immunophilin FKBP52 in motor coordination. Behav Brain Res 313:97–110. https://doi.org/10.1016/j.bbr.2016.07.0155CrossRefPubMed

38.

Calderón J, Flores P, Aguirre JM, Valdivia G, Padilla O, Barra I, Scoriels L, Herrera S, González A, Massardo L (2017) Impact of cognitive impairment, depression, disease activity, and disease damage on quality of life in women with systemic lupus erythematosus. Scand J Rheumatol 46(4):273–280. https://doi.org/10.1080/03009742.2016.1206617CrossRefPubMed

39.

Elera-Fitzcarrald C, Alva M, Gamboa-Cardenas R, Mora-Trujillo CS, Zevallos F, García-Poma A, Medina M, Rodriguez-Bellido Z, Perich-Campos RA, Pastor-Asurza CA, Segami MI, Ugarte-Gil MF (2018) Factors associated with health-related quality of life in Peruvian patients with systemic lupus erythematosus. Lupus 27(6):913–919. https://doi.org/10.1177/0961203317751062CrossRefPubMed

40.

Alexander K, Conley YP, Levine JD, Cooper BA, Paul SM, Mastick J, West C, Miaskowski C (2018) Cytokine gene polymorphisms associated with various domains of quality of life in women with breast cancer. J Pain Symptom Manag 55(2):334–350.e3. https://doi.org/10.1016/j.jpainsymman.2017.09.020CrossRef

41.

Vieira DA, da Cunha LR, da Silva CB, Almeida MTB, Gomes AD, de Faria CLL, Teixeira R, Neves FS, Rocha GA, de Melo FF et al (2019) The combined polymorphisms of interleukin-6-174GG genotype and interleukin-10 ATA haplotype are associated with a poor quality of life in patients with chronic hepatitis C. Qual Life Res 28(6):1531–1542. https://doi.org/10.1007/s11136-019-02129-5CrossRefPubMed

42.

Hauer D, Weis F, Papassotiropoulos A, Schmoeckel M, Beiras-FernandezA LJ, Kaufmann I, Kirchhoff F, Vogeser M, Roozendaal B et al (2011) Relationship of a common polymorphism of the glucocorticoid receptor gene to traumatic memories and posttraumatic stress disorder in patients after intensive care therapy. Crit Care Med 39(4):643–650. https://doi.org/10.1097/CCM.0b013e318206bae6CrossRefPubMed

43.

Kästle M, Kistler B, Lamla T, Bretschneider T, Lamb D, Nicklin P, Wyatt D (2018) FKBP51 modulates steroid sensitivity and NFκB signalling: a novel anti-inflammatory drug target. Eur J Immunol 48(11):1904–1914. https://doi.org/10.1002/eji.201847699CrossRefPubMedPubMedCentral

44.

Yu HM, Wang Q, Sun WB (2017) Silencing of FKBP51 alleviates the mechanical pain threshold, inhibits DRG inflammatory factors and pain mediators through the NF-kappaB signaling pathway. Gene 627:169–175. https://doi.org/10.1016/j.gene.2017.06.029CrossRefPubMed

45.

Schoormans D, Radonic T, de Witte P, Groenink M, Azim D, Lutter R, Mulder BJM, Sprangers MAG, Zwinderman AH (2012) Mental quality of life is related to a cytokine genetic pathway. PLoS One 7(9):e45126. https://doi.org/10.1371/journal.pone.0045126CrossRefPubMedPubMedCentral

46.

Choi ST, Kang JI, Park I-H, Lee YW, Song JS, Park YB, Lee SK (2012) Subscale analysis of quality of life in patients with systemic lupus erythematosus: association with depression, fatigue, disease activity and damage. Clin Exp Rheumatol 30(5):665–672PubMed

47.

Judd LL, Schettler PJ, Brown ES, Wolkowitz OM, Sternberg EM, Bender BG, Bulloch K, Cidlowski JA, de Kloet ER, Fardet L et al (2014) Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry 171(10):1045–1051. https://doi.org/10.1176/appi.ajp.2014.13091264CrossRefPubMed

Titel: Associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in systemic lupus erythematosus patients
verfasst von: Qiu-Yue Lou
Zhen Li
Ying Teng
Qiao-Mei Xie
Man Zhang
Shun-Wei Huang
Wen-Fei Li
Yang-Fan Chen
Fa-Ming Pan
Sheng-Qian Xu
Jing Cai
Shuang Liu
Jin-Hui Tao
Sheng-Xiu Liu
Hai-Liang Huang
Fang Wang
Hai-Feng Pan
Hong Su
Zhi-Wei Xu
Wen-Biao Hu
Yan-Feng Zou
Publikationsdatum: 16.06.2020
Verlag: Springer International Publishing
Erschienen in: Clinical Rheumatology / Ausgabe 1/2021
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-020-05195-0

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Associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in systemic lupus erythematosus patients

Abstract

Objectives

Methods

Results

Conclusions

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