Jing-Wen Ai1, Hanyue Zhang1, Zumo Zhou2, Shanshan Weng1, Heqing Huang2, Sen Wang1, Lingyun Shao1, Yan Gao1, Jing Wu1, Qiaoling Ruan1, Feifei Wang1, Ning Jiang3, Jiazhen Chen4, Wenhong Zhang5. 1. Department of Infectious Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China. 2. Department of Infectious Diseases, People's Hospital of Zhuji, 122 Huanshan South Road, Zhuji, 311800, China. 3. State Key Laboratory of Genetic Engineering and Institute of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China. ningjiang@fudan.edu.cn. 4. Department of Infectious Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China. jiazhen_chen@163.com. 5. Department of Infectious Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China. wenhongzhang_hs@126.com.
Abstract
BACKGROUND: When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood. METHODS: Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases. RESULTS: We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients. CONCLUSION: We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.
BACKGROUND: When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood. METHODS: Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases. RESULTS: We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients. CONCLUSION: We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.
Entities:
Keywords:
Active tuberculosis infection; Expression quantitative trait loci; Genetic susceptibility; Latent tuberculosis; Single nucleotide polymorphisms
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