端粒酶基因多态性而非端粒长度增加了女性患原发性肾小球肾炎/终末期肾病的易感性。
The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females.
作者信息
Sun Qing, Liu Junli, Cheng Guanghui, Dai Mingkai, Liu Jiaxi, Qi Zhenqiang, Zhao Jingjie, Li Wei, Kong Feng, Liu Gang, Björkholm Magnus, Xu Dawei
机构信息
Central Research Laboratory, Shandong University Second Hospital, Jinan, 250035, People's Republic of China.
Laboratory for Molecular Diagnostics, Shandong University Second Hospital, Jinan, 250035, People's Republic of China.
出版信息
J Transl Med. 2020 May 4;18(1):184. doi: 10.1186/s12967-020-02347-3.
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.
背景
原发性肾小球肾炎（GN）是慢性肾脏病（CKD）的主要病因，且常进展为终末期肾病（ESRD）。较短的白细胞端粒长度（LTL）与CKD易感性及肾功能减退有关，然而，端粒酶基因变异是否会增加GN/CKD/ESRD风险尚不清楚。在此，我们通过确定它们与端粒酶RNA组分（TERC）的rs12696304及端粒酶逆转录酶（TERT）基因座的rs2736100基因变异的关联来解决这一问题。
方法
该研究纳入769例患者（243例原发性GN衍生的CKD患者及526例ESRD患者）以及性别和年龄匹配的健康对照。从对照和患者的外周血中提取基因组DNA。使用基于PCR的检测方法对rs12696304和rs2736100变异进行基因分型。采用定量PCR（qPCR）测定白细胞端粒长度（LTL）。
结果
在患者中观察到TERC rs12696304 G等位基因频率显著更高，且与疾病风险增加相关（C与G比较：OR = 1.334，95% CI 1.112 - 1.586，P = 0.001；CC + GC与GG比较：OR = 1.334，95% CI 1.122 - 1.586，P = 0.001）。进一步分析表明，这种显著差异仅存在于女性对照与患者之间（C与G比较：OR = 1.483，95% CI 1.140 - 1.929，P = 0.003；CC + GC与CC比较：OR = 1.692，95% CI 1.202 - 2.383，P = 0.003），男性中则无此差异。对照与患者之间rs2736100变异无差异，但女性ESRD患者携带的C等位基因频率显著高于女性对照（A与C比较：OR = 1.306，95% CI 1.005 - 1.698，P = 0.046；AA与CC比较：OR = 1.781，95% CI 1.033 - 3.070，P = 0.037）。对照与患者之间LTL无差异。
结论
我们的结果表明，TERC rs12696304和TERT rs2736100多态性而非LTL本身会增加GN/CDK/ESRD风险。
Zotero 插件