title: Changes in the expression of telomere maintenance genes might play a role in the pathogenesis of systemic lupus erythematosus.
abstract: Previous studies demonstrated that telomerase activity increased while telomere length shortened in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). This study aimed to examine the changes of telomere maintenance genes and their clinical significance in SLE. The mRNA level of telomeric proteins in PBMCs, including shelterin complex (TRF1, TRF2, POT1, TPP1, TIN2 and hRAP1), a set of multifunctional proteins involved in telomere maintenance (MRE11, KU80 and RPA1), and Ki67, was measured using real-time quantitative PCR in 56 SLE patients (36 treated and 20 untreated; 32 with renal involvement and 24 without renal involvement) and 46 healthy subjects (controls). The expression of TPP1, TIN2, POT1 and KU80 was significantly reduced while that of TRF2 and MRE11 increased in SLE patients (p < 0.05, respectively); significant difference was not found in the expression of TRF1, hRAP1, RPA1 and Ki67 (p > 0.05, respectively). The expression of TRF2, MRE11 and Ki67 was much higher in untreated SLE patients than in controls or treated SLE patients (p < 0.05, respectively); the expression of hRAP1 was much higher in SLE patients with renal involvement than in controls or SLE patients without renal involvement (p < 0.05, respectively). Significant positive correlation was found between level of KU80 and C3, TPP1 and TIN2, TPP1 and POT1, while significant negative correlation was found between KU80 and serum total globulins, TIN2 and RF, TPP1 and SLEDAI score (p < 0.05, respectively). In conclusion, altered expression of telomere maintenance genes might be involved in the pathogenesis of SLE. Further study in expression and functions of telomeric proteins would be needed.
authors.affiliation: Institute of Rheumatology and Immunology and Department of Rheumatology of the Affiliated Hospital, North Sichuan Medical College, Sichuan, China. jgzhou@nsmc.edu.cn
authors.forename: J G
authors.initials: JG
authors.lastname: Zhou
authors.forename: Y F
authors.initials: YF
authors.lastname: Qing
authors.forename: Q B
authors.initials: QB
authors.lastname: Yang
authors.forename: W G
authors.initials: WG
authors.lastname: Xie
authors.forename: M C
authors.initials: MC
authors.lastname: Zhao
mesh_terms: D000328:Adult; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D000072200:Ku Autoantigen; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D000076228:MRE11 Homologue Protein; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D000089804:Shelterin Complex; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C495876:ACD protein, human; D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; C121766:MRE11 protein, human; C440849:POT1 protein, human; D012333:RNA, Messenger; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D019098:Telomerase; D000076228:MRE11 Homologue Protein; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen