Cargando…

A Common Variant of ASAP1 Is Associated with Tuberculosis Susceptibility in the Han Chinese Population

BACKGROUND: ASAP1 (also known as AMAP1 or DDEF1) encodes an Arf GTPase-activating protein (Arf GAP), a multifunctional scaffold protein that induces hydrolysis of GTP bound to the ADP-ribosylation factor (Arf) family GTP-binding proteins. Reduction of ASAP1 expression in vitro was related to suppres...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Cheng, Zhao, Qi, Shao, Yan, Li, Yan, Song, Honghuan, Li, Guoli, Zhu, Limei, Lu, Wei, Xu, Biao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476032/
https://www.ncbi.nlm.nih.gov/pubmed/31089398
http://dx.doi.org/10.1155/2019/7945429
_version_ 1783412836145299456
author Chen, Cheng
Zhao, Qi
Shao, Yan
Li, Yan
Song, Honghuan
Li, Guoli
Zhu, Limei
Lu, Wei
Xu, Biao
author_facet Chen, Cheng
Zhao, Qi
Shao, Yan
Li, Yan
Song, Honghuan
Li, Guoli
Zhu, Limei
Lu, Wei
Xu, Biao
author_sort Chen, Cheng
collection PubMed
description BACKGROUND: ASAP1 (also known as AMAP1 or DDEF1) encodes an Arf GTPase-activating protein (Arf GAP), a multifunctional scaffold protein that induces hydrolysis of GTP bound to the ADP-ribosylation factor (Arf) family GTP-binding proteins. Reduction of ASAP1 expression in vitro was related to suppression of cell migration and invasiveness. The genetic variant rs4733781 of the ASAP1 gene was revealed as a significant locus for tuberculosis (TB) susceptibility, but the results still need to be validated. METHODS: Blood samples from a total of 1914 active TB and healthy controls (HC) were collected to evaluate rs4733781 and the risk of TB. Meanwhile, a total of 48 noninfected HC, latent TB-infected (LTBI) controls, and active TB were collected to assay ASAP1 expression difference among the three groups. The QuantiFERON-TB Gold In-Tube was adopted to identify noninfected HC and LTBI. RESULTS: The genetic variant of rs4733781 was found to be significantly associated with TB, and the A allele of rs4733781 (C>A) was 0.38 and 0.43 among TB cases and HC, respectively (P = 0.0035). Meanwhile, the peripheral blood monocyte RNA fold changes for the ASAP1 gene among the 16 HC, 16 LTBI, and 16 active TB were 1.088 ± 0.4919, 2.237 ± 0.6505, and 10.12 ± 10.98 (F = 9.559, P = 0.0003), respectively, and the expression of ASAP1 was increased by 2.06-fold (P < 0.0001) and 9.30-fold (P < 0.0052) for LTBI and active TB, when compared to the HC. CONCLUSIONS: Our data indicated that the A allele of rs4733781 for the ASAP1 gene was in association with a decreased risk of TB. But not only that, the overexpression of the ASAP1 gene among LTBI and TB was related to the progression of TB, which further implies that the expression of ASAP1 would be a potential biomarker for LTBI and TB diagnoses.
format Online
Article
Text
id pubmed-6476032
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-64760322019-05-14 A Common Variant of ASAP1 Is Associated with Tuberculosis Susceptibility in the Han Chinese Population Chen, Cheng Zhao, Qi Shao, Yan Li, Yan Song, Honghuan Li, Guoli Zhu, Limei Lu, Wei Xu, Biao Dis Markers Research Article BACKGROUND: ASAP1 (also known as AMAP1 or DDEF1) encodes an Arf GTPase-activating protein (Arf GAP), a multifunctional scaffold protein that induces hydrolysis of GTP bound to the ADP-ribosylation factor (Arf) family GTP-binding proteins. Reduction of ASAP1 expression in vitro was related to suppression of cell migration and invasiveness. The genetic variant rs4733781 of the ASAP1 gene was revealed as a significant locus for tuberculosis (TB) susceptibility, but the results still need to be validated. METHODS: Blood samples from a total of 1914 active TB and healthy controls (HC) were collected to evaluate rs4733781 and the risk of TB. Meanwhile, a total of 48 noninfected HC, latent TB-infected (LTBI) controls, and active TB were collected to assay ASAP1 expression difference among the three groups. The QuantiFERON-TB Gold In-Tube was adopted to identify noninfected HC and LTBI. RESULTS: The genetic variant of rs4733781 was found to be significantly associated with TB, and the A allele of rs4733781 (C>A) was 0.38 and 0.43 among TB cases and HC, respectively (P = 0.0035). Meanwhile, the peripheral blood monocyte RNA fold changes for the ASAP1 gene among the 16 HC, 16 LTBI, and 16 active TB were 1.088 ± 0.4919, 2.237 ± 0.6505, and 10.12 ± 10.98 (F = 9.559, P = 0.0003), respectively, and the expression of ASAP1 was increased by 2.06-fold (P < 0.0001) and 9.30-fold (P < 0.0052) for LTBI and active TB, when compared to the HC. CONCLUSIONS: Our data indicated that the A allele of rs4733781 for the ASAP1 gene was in association with a decreased risk of TB. But not only that, the overexpression of the ASAP1 gene among LTBI and TB was related to the progression of TB, which further implies that the expression of ASAP1 would be a potential biomarker for LTBI and TB diagnoses. Hindawi 2019-04-08 /pmc/articles/PMC6476032/ /pubmed/31089398 http://dx.doi.org/10.1155/2019/7945429 Text en Copyright © 2019 Cheng Chen et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chen, Cheng
Zhao, Qi
Shao, Yan
Li, Yan
Song, Honghuan
Li, Guoli
Zhu, Limei
Lu, Wei
Xu, Biao
A Common Variant of ASAP1 Is Associated with Tuberculosis Susceptibility in the Han Chinese Population
title A Common Variant of ASAP1 Is Associated with Tuberculosis Susceptibility in the Han Chinese Population
title_full A Common Variant of ASAP1 Is Associated with Tuberculosis Susceptibility in the Han Chinese Population
title_fullStr A Common Variant of ASAP1 Is Associated with Tuberculosis Susceptibility in the Han Chinese Population
title_full_unstemmed A Common Variant of ASAP1 Is Associated with Tuberculosis Susceptibility in the Han Chinese Population
title_short A Common Variant of ASAP1 Is Associated with Tuberculosis Susceptibility in the Han Chinese Population
title_sort common variant of asap1 is associated with tuberculosis susceptibility in the han chinese population
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476032/
https://www.ncbi.nlm.nih.gov/pubmed/31089398
http://dx.doi.org/10.1155/2019/7945429
work_keys_str_mv AT chencheng acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT zhaoqi acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT shaoyan acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT liyan acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT songhonghuan acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT liguoli acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT zhulimei acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT luwei acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT xubiao acommonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT chencheng commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT zhaoqi commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT shaoyan commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT liyan commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT songhonghuan commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT liguoli commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT zhulimei commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT luwei commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation
AT xubiao commonvariantofasap1isassociatedwithtuberculosissusceptibilityinthehanchinesepopulation