West China School of Medicine, Sichuan University, Chengdu, China.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
J Clin Lab Anal. 2021 Feb;35(2):e23630. doi: 10.1002/jcla.23630. Epub 2020 Dec 9.
The role of collagen type XVIII alpha 1 chain (COL18A1) in anti-tuberculosis drug-induced hepatotoxicity (ATDH) has not been reported. This study aimed to explore the association between of COL18A1 variants and ATDH susceptibility.
A total of 746 patients were enrolled in our study from December 2016 to April 2018, and all subjects in the study signed an informed consent form. The custom-by-design 2x48-Plex SNPscanTM kit was used to genotype all selected 11 SNPs. Categorical variables were compared by chi-square (χ ) or Fisher's exact test, while continuous variables were compared by Mann-Whitney's U test. Plink was utilized to analyze allelic and genotypic frequencies, and genetic models. Multivariate logistic regression analyses were used to adjust potential factors. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were also calculated.
Among patients with successfully genotyping, there were 114 cases and 612 controls. The mutant A allele of rs12483377 conferred the decreased risk of ATDH (OR = 0.13, 95%CI: 0.02-0.98, P = 0.020), and this significance still existed after adjusting age and gender (P = 0.024). The mutant homozygote AA genotype of rs12483377 was associated with decreased total protein levels (P = 0.018).
Our study first revealed that the A allele of COL18A1 rs12483377 was associated with the decreased risk of ATDH in the Western Chinese Han population, providing new perspective for the molecular prediction, precise diagnosis, and individual treatment of ATDH.
胶原 XVIII 型 α1 链（COL18A1）在抗结核药物性肝损伤（ATDH）中的作用尚未报道。本研究旨在探讨 COL18A1 变异与 ATDH 易感性的关系。
本研究共纳入 2016 年 12 月至 2018 年 4 月的 746 例患者，所有研究对象均签署知情同意书。使用定制的 2x48-Plex SNPscanTM 试剂盒对所有选定的 11 个 SNP 进行基因分型。采用卡方（χ ）或 Fisher 确切检验比较分类变量，采用 Mann-Whitney U 检验比较连续变量。采用 Plink 分析等位基因和基因型频率及遗传模型。采用多变量 logistic 回归分析调整潜在因素。计算比值比（OR）及其 95%置信区间（CI）。
在成功进行基因分型的患者中，有 114 例和 612 例对照。rs12483377 的突变 A 等位基因降低了 ATDH 的发病风险（OR=0.13，95%CI：0.02-0.98，P=0.020），且在调整年龄和性别后仍有统计学意义（P=0.024）。rs12483377 的突变纯合子 AA 基因型与总蛋白水平降低有关（P=0.018）。
本研究首次表明，COL18A1 rs12483377 的 A 等位基因与西方汉族人群 ATDH 的发病风险降低相关，为 ATDH 的分子预测、精准诊断和个体化治疗提供了新视角。
