The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females
Abstract Background Primary glomerulonephritis (GN) is the leading cause of chronic kidney disease (CKD) and frequently progresses into end stage renal diseases (ESRDs). Shorter leukocyte telomere length (LTL) has been implicated in the CKD susceptibility and diminished kidney function, however, it...
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doaj-3b775d2a94ce4f87a3c00b5666fc49cf2020-11-25T02:59:14ZengBMCJournal of Translational Medicine1479-58762020-05-0118111110.1186/s12967-020-02347-3The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in femalesQing Sun0Junli Liu1Guanghui Cheng2Mingkai Dai3Jiaxi Liu4Zhenqiang Qi5Jingjie Zhao6Wei Li7Feng Kong8Gang Liu9Magnus Björkholm10Dawei Xu11Central Research Laboratory, Shandong University Second HospitalLaboratory for Molecular Diagnostics, Shandong University Second HospitalCentral Research Laboratory, Shandong University Second HospitalCentral Research Laboratory, Shandong University Second HospitalCentral Research Laboratory, Shandong University Second HospitalDepartment of Nephrology, Affiliated Hospital of Shandong University of Traditional Chinese MedicineLaboratory for Molecular Diagnostics, Shandong University Second HospitalDepartment of Nephrology, Affiliated Hospital of Shandong University of Traditional Chinese MedicineCentral Research Laboratory, Shandong University Second HospitalNephrology Research Institute of Shandong University, Shandong University Second HospitalDepartment of Medicine, Center for Molecular Medicine and Bioclinicum, Karolinska Institutet, Karolinska University Hospital SolnaDepartment of Medicine, Center for Molecular Medicine and Bioclinicum, Karolinska Institutet, Karolinska University Hospital SolnaAbstract Background Primary glomerulonephritis (GN) is the leading cause of chronic kidney disease (CKD) and frequently progresses into end stage renal diseases (ESRDs). Shorter leukocyte telomere length (LTL) has been implicated in the CKD susceptibility and diminished kidney function, however, it is unclear whether the variants in telomerase genes contribute to risk to GN/CKD/ESRD. Here we address this issue by determining their association with the genetic variants of rs12696304 at the telomerase RNA component (TERC) and rs2736100 at the telomerase reverse transcriptase (TERT) loci. Methods The study includes 769 patients (243 primary GN-derived CKD and 526 ESRD cases) and sex-/age-matched healthy controls. Genomic DNA was extracted from peripheral blood of both controls and patients. Genotyping of rs12696304 and rs2736100 variants was carried out using PCR-based assays. Leukocyte telomere length (LTL) was determined using quantitative PCR (qPCR). Results A significantly higher frequency of TERC rs12696304 G allele was observed in patients and associated with increased disease risk (C vs G: OR = 1.334, 95% CI 1.112–1.586, P = 0.001; CC + GC vs GG: OR = 1.334, 95% CI 1.122–1.586, P = 0.001). Further analyses showed that such significant differences were only present between female controls and patients (C vs G: OR = 1.483, 95% CI 1.140–1.929, P = 0.003; CC + GC vs CC: OR = 1.692, 95% CI 1.202–2.383, P = 0.003), but not males. There were no differences in rs2736100 variants between controls and patients, but female ESRD patients carried significantly higher C allele frequencies than did female controls (A vs C: OR = 1.306, 95% CI 1.005–1.698, P = 0.046; AA vs CC: OR = 1.781, 95% CI 1.033–3.070, P = 0.037). There was no difference in LTL between controls and patients. Conclusions Our results reveal that the TERC rs12696304 and TERT rs2736100 polymorphisms, but not LTL per se, contribute to GN/CDK/ESRD risk.http://link.springer.com/article/10.1186/s12967-020-02347-3CKDGenotypesGlomerulonephritisSingle nucleotide polymorphismTelomeraseTelomere |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qing Sun Junli Liu Guanghui Cheng Mingkai Dai Jiaxi Liu Zhenqiang Qi Jingjie Zhao Wei Li Feng Kong Gang Liu Magnus Björkholm Dawei Xu |
spellingShingle |
Qing Sun Junli Liu Guanghui Cheng Mingkai Dai Jiaxi Liu Zhenqiang Qi Jingjie Zhao Wei Li Feng Kong Gang Liu Magnus Björkholm Dawei Xu The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females Journal of Translational Medicine CKD Genotypes Glomerulonephritis Single nucleotide polymorphism Telomerase Telomere |
author_facet |
Qing Sun Junli Liu Guanghui Cheng Mingkai Dai Jiaxi Liu Zhenqiang Qi Jingjie Zhao Wei Li Feng Kong Gang Liu Magnus Björkholm Dawei Xu |
author_sort |
Qing Sun |
title |
The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females |
title_short |
The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females |
title_full |
The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females |
title_fullStr |
The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females |
title_full_unstemmed |
The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females |
title_sort |
telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2020-05-01 |
description |
Abstract Background Primary glomerulonephritis (GN) is the leading cause of chronic kidney disease (CKD) and frequently progresses into end stage renal diseases (ESRDs). Shorter leukocyte telomere length (LTL) has been implicated in the CKD susceptibility and diminished kidney function, however, it is unclear whether the variants in telomerase genes contribute to risk to GN/CKD/ESRD. Here we address this issue by determining their association with the genetic variants of rs12696304 at the telomerase RNA component (TERC) and rs2736100 at the telomerase reverse transcriptase (TERT) loci. Methods The study includes 769 patients (243 primary GN-derived CKD and 526 ESRD cases) and sex-/age-matched healthy controls. Genomic DNA was extracted from peripheral blood of both controls and patients. Genotyping of rs12696304 and rs2736100 variants was carried out using PCR-based assays. Leukocyte telomere length (LTL) was determined using quantitative PCR (qPCR). Results A significantly higher frequency of TERC rs12696304 G allele was observed in patients and associated with increased disease risk (C vs G: OR = 1.334, 95% CI 1.112–1.586, P = 0.001; CC + GC vs GG: OR = 1.334, 95% CI 1.122–1.586, P = 0.001). Further analyses showed that such significant differences were only present between female controls and patients (C vs G: OR = 1.483, 95% CI 1.140–1.929, P = 0.003; CC + GC vs CC: OR = 1.692, 95% CI 1.202–2.383, P = 0.003), but not males. There were no differences in rs2736100 variants between controls and patients, but female ESRD patients carried significantly higher C allele frequencies than did female controls (A vs C: OR = 1.306, 95% CI 1.005–1.698, P = 0.046; AA vs CC: OR = 1.781, 95% CI 1.033–3.070, P = 0.037). There was no difference in LTL between controls and patients. Conclusions Our results reveal that the TERC rs12696304 and TERT rs2736100 polymorphisms, but not LTL per se, contribute to GN/CDK/ESRD risk. |
topic |
CKD Genotypes Glomerulonephritis Single nucleotide polymorphism Telomerase Telomere |
url |
http://link.springer.com/article/10.1186/s12967-020-02347-3 |
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