scholarly journals Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yuan-yuan Qi ◽  
Xin-ran Liu ◽  
Ying-xin He ◽  
Min Zhou ◽  
Xiang-hui Ning ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Genetic Association ◽  
Lupus Erythematosus ◽  
Genome Wide Association Study ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Chinese Populations ◽  
Genetic Heritability

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.

Detection and Functional Evaluation of −262A/T and −188A/G Polymorphisms of SLAM Gene in Patients with Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (11) ◽  
pp. 2268-2272 ◽  
Author(s):  
YI YOU ◽  
ZHE WANG ◽  
GUO-HONG DENG ◽  
YI LIU ◽  
FEI HAO
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Chinese Patients ◽  
Luciferase Reporter ◽  
Functional Evaluation ◽  
Reporter System ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear

Objective.Signaling lymphocytic activation molecule (SLAM) has been related to the pathology of systemic lupus erythematosus (SLE) through regulation of T cell-dependent humoral immune responses. We investigated the functional associations of the −262A/T and −188A/G polymorphisms of SLAM in Chinese patients with SLE.Methods.Genotyping of −262A/T (rs2295614) and −188A/G (rs2295613) in SLAM was carried out in 248 cases and 278 controls. Promoter activities of haplotypes on the SLAM gene were evaluated with the dual-luciferase reporter system. The mRNA expressions of SLAM on peripheral blood mononuclear cells (PBMC) of SLE patients with different genotypes were determined by real-time polymerase chain reaction.Results.Frequencies of −262A allele and −188G allele were significantly higher in SLE patients than in controls. Haplotype analysis and multifactorial logistic regression analysis showed that individuals with the AG/AG haplotype had increased susceptibility to SLE (p = 0.002, OR 1.478, 95% CI 1.152–1.897). In response to PHA stimulation, the SLAM mRNA expression on PBMC of SLE patients was significantly higher in −262A-188G haplotype homozygotes compared with −262A-188G heterozygotes and individuals with other genotypes.Conclusion.Our findings suggest that −262A-188G haplotype in the SLAM gene promoter contributes to the risk of SLE by increasing the expression of SLAM.

Genomewide analysis of 6-methyladenine DNA in peripheral blood mononuclear cells of systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 359-364 ◽  
Author(s):  
F Zheng ◽  
D Tang ◽  
H Xu ◽  
Y Xu ◽  
W Dai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Peripheral Blood Mononuclear Cells ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Initial Development ◽  
Blood Mononuclear Cells ◽  
High Level

Aim The aim of this paper is to explore the expression of 6-methyladenine (6mA) DNA and to elucidate its gene regulation role in systemic lupus erythematosus (SLE). Methods Twenty SLE patients and 20 normal control healthy individuals (HCs) were included in this study. Genomic DNA was isolated from peripheral blood mononuclear cells and subsequently underwent 6mA-immunoprecipitation-sequencing (6mA-IP-Seq) after DNA quality control and 6mA precipitation. Bioinformation analysis was applied to the raw data comparing 6mA levels between SLE patients and HCs. Results We identified 5462 hypermethylation and 431 hypomethylation genes in PBMCs of individuals with SLE, which indicated that a high level of 6mA participates in the pathogenesis of SLE. Gene ontology analysis revealed that hypermethylation genes might regulate the inflammatory process, which has been well documented in the pathogenesis of SLE. Conclusion 6mA may be involved in the initial development of SLE, which may lead to its potential use as an early diagnostic marker and therapeutic target.

scholarly journals Belimumab alters transitional B-cell subset proportions in patients with stable systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (11) ◽  
pp. 1337-1343 ◽  
Author(s):  
A Benitez ◽  
K Torralba ◽  
M Ngo ◽  
L M Salto ◽  
K S Choi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Cell Subset ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Immature B Cells

Objective We evaluated the effects of the B-cell activating factor (BAFF)-targeting antibody Belimumab on human nonmemory B-cell pools. Human B-cell pools were identified using surface markers adapted from mouse studies that specifically assessed reductions in immature B cells due to BAFF depletion. Patients with systemic lupus erythematosus (SLE) have high levels of both BAFF and immature B cells. Mechanistic mouse studies provide a framework for understanding human responses to therapies that target B cells. Methods Peripheral blood mononuclear cells were isolated from healthy donors and SLE patients on Belimumab or standard-of-care therapy (SCT). Cells were stained for flow cytometry to identify B-cell subsets based on CD21/CD24. Differences in subset proportions were determined by one-way ANOVA and Tukey’s post hoc test. Results Patients treated with Belimumab show alterations in the nonmemory B-cell pool characterized by a decrease in the Transitional 2 (T2) subset ( p = 0.002), and an increase in the proportion of Transitional 1 (T1) cells ( p = 0.005) as compared with healthy donors and SCT patients. The naïve B-cell compartment showed no significant differences between the groups ( p = 0.293). Conclusion Using a translational approach, we show that Belimumab-mediated BAFF depletion reduces the T2 subset in patients, similar to observations in mouse models with BAFF depletion.

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