1. Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations
- Author
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Xin-Ran Liu, Zhanzheng Zhao, Xiaoxue Zhang, Ya-Fei Zhao, Yuan-yuan Qi, Xiang-Hui Ning, Xiaoyang Wang, Ying-Xin He, Min Zhou, Yaling Zhai, and Yan Cui
- Subjects
0301 basic medicine ,Adult ,Male ,Telomerase ,China ,Article Subject ,Adolescent ,Immunology ,Single-nucleotide polymorphism ,Genome-wide association study ,Cell Cycle Proteins ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Asian People ,Immunology and Allergy ,Humans ,Lupus Erythematosus, Systemic ,Telomerase reverse transcriptase ,Genetic Predisposition to Disease ,PINX1 ,Allele ,Genetic association ,030203 arthritis & rheumatology ,Genetics ,Tumor Suppressor Proteins ,Telomere Homeostasis ,General Medicine ,RC581-607 ,Telomere ,030104 developmental biology ,Case-Control Studies ,Female ,Immunologic diseases. Allergy ,Research Article ,Genome-Wide Association Study - Abstract
A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (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 PINX1 rs6984094 was identified ( P discovery = 4.13 × 10 − 2 , OR = 0.58 , 95% CI 0.35-0.98) and successfully replicated ( P replication = 5.73 × 10 − 3 , OR = 0.45 , 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the PINX1 rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of PINX1 mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between PINX1 (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations.
- Published
- 2021