Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations.
J Immunol Res
; 2021: 7079359, 2021.
Article
in En
| MEDLINE
| ID: mdl-34337078
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Cycle Proteins
/
Genetic Predisposition to Disease
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Tumor Suppressor Proteins
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Lupus Erythematosus, Systemic
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Adolescent
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Adult
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Female
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Humans
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Male
Country/Region as subject:
Asia
Language:
En
Journal:
J Immunol Res
Year:
2021
Document type:
Article
Affiliation country:
Country of publication:
EG
/
EGIPTO
/
EGITO
/
EGYPT