Prospective study of ALDH1A1 gene polymorphisms associated with antituberculosis drug-induced liver injury in Western Chinese Han population.

Antituberculosis drug-induced liver injury (ATDILI) has received increasing attention globally, which may limit the effectiveness of the anti-tuberculosis (anti-TB) treatment. Many host genetic determinants of ATDILI have been identified, recently. Whereas, little knowledge about the association between aldehyde dehydrogenase 1 family member A1 (ALDH1A1) polymorphisms and ATDILI is currently available, so we investigated the association between their variants and the susceptibility to ATDILI. A total of 747 TB patients treated by first-line antituberculosis drugs were prospectively enrolled at West China Hospital. Genomic DNA was extracted from the peripheral blood sample of each patient and 7 single-nucleotide polymorphisms (SNPs) of ALDH1A1 gene were screened and genotyped with a custom-designed 2x48-plex SNP Scan TM Kit. The patients were followed up monthly to monitor the development of ATDILI. The C allele and the CA genotype of rs7852860 was significantly associated with an elevated risk for ATDILI (p = 0.006 and 0.005, respectively), which was consistent with the results in the dominant and additive models. No allele, genotype or genetic model of the other 6 SNPs (rs3764435, rs348471, rs63319, rs610529, rs7027604, rs8187876) were found to be associated with the susceptibility to ATDILI. Our findings firstly demonstate that rs7852860 variants in ALDH1A1 gene is associated with susceptibility to ATDILI in the Chinese Han population. Validation studies with larger sample sizes and other ethnic groups are needed to confirm our findings. This article is protected by copyright. All rights reserved.