Association between NOS 2 gene polymorphisms and susceptibility of anti-tuberculous drug induced liver injury / 中华传染病杂志

ABSTRACT

Objective Inducible isoform of NO synthase(iNOS),coded by NOS2,is one of the antioxidant enzymes. The aim of this study is to explore the association between NOS2 gene polymorphisms and susceptibility of anti-tuberculous drug induced liver injury(ATDILI).Methods Sixteen tagSNP of NOS2 gene were selected using systematic bioinformatic analysis(HWE-P> 0.001, MAF>0.1,r2>0.8).A population based case-control study was performed to genotype 16 tagSNP of NOS2 gene in 461 ATDILI patients and 466 non-ATDILI patients using SNPscanTMtechnology.The genotype and haplotype frequencies were compared between case and control groups.Three genetic models including dominant,recessive and additive models were used to analyze the association between all the selected SNP polymorphisms and susceptibility of ATDILI.Results All the alleles frequencies of these SNP were in Hardy-Weinberg equilibrium.NOS2 rs9906835 G/A genotype,rs944725 T/C genotype, rs3794763 G/A genotype,rs3794764 G/A and A/A genotype,rs6505469 T/A genotype were associated with increased risk for developing ATDILI(all P< 0.05).NOS2 rs9906835,rs944725,rs3794763, rs3794764 and rs6505469 were associated with susceptibility of ATDILI in dominant model(all P<0.05).NOS2 rs944725,rs3794763 and rs3794764 were associated with increased risk for developing ATDILI in recessive model(all P< 0.05).In addition,CGCATT,AC and AAA haplotypes of NOS2 gene were found to have association with susceptibility of ATDILI(all P<0.05).Conclusion Our study showed that NOS2 gene is a susceptible gene of ATDILI.