The relationship between polymorphisms of N-acetyltransferase 2 genes and anti-tuberculosis drug induced hepatic-injury / 中华传染病杂志

ABSTRACT

Objective To investigate the relationship between polymorphisms of N-acetyltransferase 2(NAT2)genes and anti-tuberculosis drug induced hepatic-injury(ADIH).Methods A 11 matched case-control study was conducted.One hundred and six cases fulfilling the criteria of ADIH were selected as ADIH group from the patients who received anti-tuberculosis therapy.whereas those patients without any hepatic inj ury related elinical symptoms during three months of follow-up period were selected as control.The genetic polymorphisms of the loci,NAT2481C/T,NAT2-590G/A and NAT2-857G/A,were determined by polymerase chain reaction and restriction fragment length polymorphism technique(PCR-RFLP)in patients who received antituberculosis therapy.The major environmental factors and genotypes were analyzed by univariate and multivariate conditional Logistic analyses.Results The T,AA allele frequencies of NAT2-481C/T,NAT2-590G/A and NAT2-857G/A were 7.5%,28.8%and 17.9%respectively in ADIH group,and 6.6%,18.9%and 17.5%,respectively in the control group.Univariate analysis demonstrated that the frequency of NAT2 slow acetylation genotype in ADIH group was significantly higher than that in control group with a crude OR(95%CI)of 2.250(1.140-4.441).Among 6 potential risk factors,i.e.education level,occupation,body mass index(BMI),smoking,drinking and the type of tuberculosis,the low BMI and drinking were two risk factors for ADIH.In multivariate analysis,ADIH remained associated with acetylation genotype after adjusting for BMI and drinking status.The adjusted OR(95%CI)was 2.246(1.086-4.644).Conclusion NAT2 slow acetylation genotype may be associated with the occurrence of ADIH.