Glutathione S-transferases T1 null genotype is associated with susceptibility to aristolochic acid nephropathy.

Objectives: This study aims to determine whether six polymorphisms of the genes involved in drug metabolism are associated with susceptibility to the development and progression of aristolochic acid nephropathy (AAN).

Methods: In the study, 91 aristolochic acid nephropathy (AAN) cases and 152 healthy controls of Chinese Han population were examined. Six common polymorphisms of genes, including multidrug resistance gene 1 (MDR1), cytochrome P450 (CYP1A1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST) T1 and M1, were determined. Associations between their genotypes with AAN risk were calculated using an unconditional logistic regression model.

Results: Among the six candidate polymorphisms, only the distribution frequency of GSTT1 null genotype was significantly higher among AAN cases compared with controls (P = 0.041, 62.6% vs. 48.7%) and was associated with a 1.7-fold increased risk (OR = 1.728, 95%CI: 1.013-2.948, P = 0.045) of developing AAN, after adjustment for age and gender. The stratified analysis further showed that the GSTT1 null genotype was dominant in slow progressive AAN patients (OR = 2.497, 95%CI: 1.028-6.064, P = 0.043). The GSTM1 genotypes were not shown to influence the development of AAN.

Conclusion: This study supports the hypothesis that polymorphisms related to drug metabolism such as GSTT1 may be an important factor influencing the development of AAN in the Chinese Han population exposed to AA.