title: Glutathione S-transferases T1 null genotype is associated with susceptibility to aristolochic acid nephropathy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
authors: Bicheng
authors: B
authors: Chen
authors: Yongheng
authors: Y
authors: Bai
authors: Mei
authors: M
authors: Sun
authors: Xiaojie
authors: X
authors: Ni
authors: Yunxiu
authors: Y
authors: Yang
authors: Yirong
authors: Y
authors: Yang
authors: Shaoling
authors: S
authors: Zheng
authors: Feifei
authors: F
authors: Xu
authors: Shengchuan
authors: S
authors: Dai
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D034341:Aristolochic Acids / Q000009:adverse effects*; D044466:Asian People; D002681:China; D016001:Confidence Intervals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D034341:Aristolochic Acids; D019363:Cytochrome P-450 CYP1A1; D004365:Drugs, Chinese Herbal; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); C000228:aristolochic acid I; C447479:NQO1 protein, human; C413545:glutathione S-transferase T1