Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations.
J Immunol Res
; 2021: 7079359, 2021.
Article
em 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ciclo Celular
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Predisposição Genética para Doença
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Proteínas Supressoras de Tumor
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Lúpus Eritematoso Sistêmico
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
/
Female
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Humans
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Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Immunol Res
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China