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The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study

Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of sing...

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Autores principales: Lyu, Mengyuan, Zhou, Jian, Chen, Hao, Bai, Hao, Song, Jiajia, Liu, Tangyuheng, Cheng, Yuhui, Ying, Binwu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946452/
https://www.ncbi.nlm.nih.gov/pubmed/31689868
http://dx.doi.org/10.1097/MD.0000000000017821
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author Lyu, Mengyuan
Zhou, Jian
Chen, Hao
Bai, Hao
Song, Jiajia
Liu, Tangyuheng
Cheng, Yuhui
Ying, Binwu
author_facet Lyu, Mengyuan
Zhou, Jian
Chen, Hao
Bai, Hao
Song, Jiajia
Liu, Tangyuheng
Cheng, Yuhui
Ying, Binwu
author_sort Lyu, Mengyuan
collection PubMed
description Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI. The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated. Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (P(Bonferroni)(correction) = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686–6.139, P(Bonferroni correction) = .003) or dominant model (P(Bonferroni correction) = .003), as well as rs117806152 (Additive model: P(Bonferroni correction) = .05; dominant model: P(Bonferroni correction) = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (P(Bonferroni correction) = .02), while rs2617972 A allele conferred susceptibility to ATDILI (P(Bonferroni correction) = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487–6.896, P(Bonferroni correction) = .02) and dominant model (P(Bonferroni correction) = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13. Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI.
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spelling pubmed-69464522020-01-31 The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study Lyu, Mengyuan Zhou, Jian Chen, Hao Bai, Hao Song, Jiajia Liu, Tangyuheng Cheng, Yuhui Ying, Binwu Medicine (Baltimore) 3500 Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI. The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated. Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (P(Bonferroni)(correction) = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686–6.139, P(Bonferroni correction) = .003) or dominant model (P(Bonferroni correction) = .003), as well as rs117806152 (Additive model: P(Bonferroni correction) = .05; dominant model: P(Bonferroni correction) = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (P(Bonferroni correction) = .02), while rs2617972 A allele conferred susceptibility to ATDILI (P(Bonferroni correction) = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487–6.896, P(Bonferroni correction) = .02) and dominant model (P(Bonferroni correction) = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13. Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI. Wolters Kluwer Health 2019-11-01 /pmc/articles/PMC6946452/ /pubmed/31689868 http://dx.doi.org/10.1097/MD.0000000000017821 Text en Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0
spellingShingle 3500
Lyu, Mengyuan
Zhou, Jian
Chen, Hao
Bai, Hao
Song, Jiajia
Liu, Tangyuheng
Cheng, Yuhui
Ying, Binwu
The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study
title The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study
title_full The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study
title_fullStr The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study
title_full_unstemmed The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study
title_short The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study
title_sort genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: a prospective study
topic 3500
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946452/
https://www.ncbi.nlm.nih.gov/pubmed/31689868
http://dx.doi.org/10.1097/MD.0000000000017821
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