Up-regulated long noncoding RNA AC007128.1 and its genetic polymorphisms associated with Tuberculosis susceptibility

Hong Yan; Guoye Liu; Yuan Liang; Wei Wu; Rui Xia; Lin Jiao; Han Shen; Zhijun Jia; Qian Wang; Zhiqiang Wang; Yi Kong; Binwu Ying; Hualiang Wang; Chengbin Wang

doi:10.21037/atm-21-2724

Up-regulated long noncoding RNA AC007128.1 and its genetic polymorphisms associated with Tuberculosis susceptibility

Ann Transl Med. 2021 Jun;9(12):1018. doi: 10.21037/atm-21-2724.

Authors

Hong Yan^{1

2}, Guoye Liu³, Yuan Liang^{4

5}, Wei Wu^{5

6}, Rui Xia³, Lin Jiao⁷, Han Shen⁸, Zhijun Jia⁹, Qian Wang³, Zhiqiang Wang³, Yi Kong¹, Binwu Ying⁷, Hualiang Wang¹⁰, Chengbin Wang¹

Affiliations

¹ Department of Clinical Laboratory Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, China.
² Laboratory Medicine Center, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.
³ Department of Laboratory Medicine, Affiliated Brain Hospital of Nanjing Medical University (Chest Branch), Nanjing, China.
⁴ The Affiliated Cancer Hospital & Hepatobiliary Center, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
⁵ Department of Bioinformatics, Nanjing Medical University, Nanjing, China.
⁶ Research Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
⁷ Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
⁸ Department of Clinical Laboratory, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
⁹ Department of Nuclear Medicine, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
¹⁰ Department of Molecular Biology, Shanghai Centre for Clinical Laboratory, Shanghai, China.

Abstract

Background: Tuberculosis (TB) remains a major public health problem. Long non-coding RNAs (lncRNAs) are important regulators of gene expression. In this study, we explored the association between the expression of lncRNA AC007128.1 and TB susceptibility.

Methods: Three single-nucleotide polymorphisms (SNPs) (rs12333784, rs6463794, and rs720964) of lncRNA AC007128.1 were selected using the 1000 Genomes Project database and offline software Haploview V4.2, and were genotyped by a customized 2×48-Plex SNPscan™ Kit.

Results: We identified two differentially expressed lncRNA including AC007128.1 and AP001065.3 in comparisons of expression profiles between ATB vs. LTBI, LTBI vs. HCs, and AC700128.1 expression was specifically and significantly up-regulated in TB patients by verification of external data. Gene Ontology functional enrichment analysis and co-expression network showed up-regulated mRNA was mainly involved in negative regulation of the G protein-coupled receptor (GPCR) signaling pathway, and FPR1 and CYP27B1 were involved in the co-expression of AC007128.1. Using the 1000 Genomes Project, software Haploview V4.2, and SNP genotype, we screened out SNP rs12333784 which locus at 7p21.3 in AC007128.1 associated with TB susceptibility. The G carrier of rs12333784 was then finally verified to be significantly associated with pulmonary TB (PTB) and extrapulmonary tuberculosis (EPTB) susceptibility (pBonferroni =0.03878), and a similar but more significant effect was observed under the dominant model analysis (pBonferroni =0.013, OR =1.349, 95% CI, 1.065-1.709). In addition, the GG + GA genotype of SNP rs12333784 was significantly correlated with higher glucose (GLU) (P=0.03), higher gamma-glutamyl transferase (GGT) (P=0.05), and higher erythrocyte sedimentation rate (ESR) (P=0.05).

Conclusions: Our findings show lncRNA AC007128.1 can be regarded as biomarkers discriminating between ATB and LTBI and may also be a diagnostic biomarker for LBTI. These findings may aid clinical decision making in the management of TB.

Keywords: AC007128.1; biomarker; genetic susceptibility; single nucleotide polymorphisms (SNPs); tuberculosis infection.