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

ABSTRACT: 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.

SUBMITTER: Chen C

PROVIDER: S-EPMC6476032 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Common Variant of <i>ASAP1</i> Is Associated with Tuberculosis Susceptibility in the Han Chinese Population.

Chen Cheng C Zhao Qi Q Shao Yan Y Li Yan Y Song Honghuan H Li Guoli G Zhu Limei L Lu Wei W Xu Biao B

Disease markers 20190408

<h4>Background</h4><i>ASAP1</i> (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 <i>ASAP1</i> expression in vitro was related to suppression of cell migration and invasiveness. The genetic variant rs4733781 of the <i>ASAP1</i> gene was revealed as a significant locus for tuberculosis (TB) susceptibility, but the r ...[more]

PMID: 31089398

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Project description:Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data.We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore.We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10-8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10-16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum.Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region.We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.

Dataset Information

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

Publications

A Common Variant of <i>ASAP1</i> Is Associated with Tuberculosis Susceptibility in the Han Chinese Population.

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