Nephrology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan 4500052, China.
School of Pharmaceutical Sciences, Zhengzhou University, 100 Ke Xue Avenue, Zhengzhou, Henan 450001, China.
J Immunol Res. 2021 Jul 13;2021:7079359. doi: 10.1155/2021/7079359. eCollection 2021.
A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of telomere. Given that only a small portion of the genetic heritability of SLE has been explained so far, we aimed to identify novel loci in telomere-related genes responsible for SLE susceptibility in Chinese populations. We performed a comprehensive genetic association analysis of SLE with telomere-related genes. To identify functional significance, we analyzed the publicly available HaploReg v4.1 and RegulomeDB databases. Differential gene expression analysis was also performed using ArrayExpress. A novel signal of rs6984094 was identified ( = 4.13 × 10, OR = 0.58, 95% CI 0.35-0.98) and successfully replicated ( = 5.73 × 10, OR = 0.45, 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations.
最近一项亚洲人群的全基因组关联研究（GWAS）报道，核苷酸多态性（SNP）与系统性红斑狼疮（SLE）相关。TERT 在维持染色体稳定性和端粒长度方面起着关键作用。鉴于迄今为止，SLE 的遗传易感性只有一小部分得到了解释，我们旨在确定与中国人群 SLE 易感性相关的端粒相关基因中的新基因座。我们对 SLE 与端粒相关基因进行了全面的遗传关联分析。为了确定功能意义，我们分析了公开的 HaploReg v4.1 和 RegulomeDB 数据库。还使用 ArrayExpress 进行了差异基因表达分析。鉴定到一个新的信号 rs6984094（ = 4.13 × 10，OR = 0.58，95% CI 0.35-0.98），并成功复制（ = 5.73 × 10，OR = 0.45，95% CI 0.26-0.81）。多层次的功能分析表明，rs6984094 风险 T 等位基因表现出增强的核蛋白结合。我们还观察到 SLE 患者外周血单核细胞中 mRNA 的表达增加。总体而言，我们观察到中国人群中 （编码 PinX1 蛋白，一种抑制端粒酶的酶，可延长端粒）与 SLE 易感性之间存在新的遗传关联。
