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

BACKGROUND

(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 expression in vitro was related to suppression of cell migration and invasiveness. The genetic variant rs4733781 of the 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 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 ( = 0.0035). Meanwhile, the peripheral blood monocyte RNA fold changes for the 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 ( = 9.559, = 0.0003), respectively, and the expression of was increased by 2.06-fold ( < 0.0001) and 9.30-fold ( < 0.0052) for LTBI and active TB, when compared to the HC.

CONCLUSIONS

Our data indicated that the A allele of rs4733781 for the gene was in association with a decreased risk of TB. But not only that, the overexpression of the gene among LTBI and TB was related to the progression of TB, which further implies that the expression of would be a potential biomarker for LTBI and TB diagnoses.