title: Analysis of silent information regulator 1 (SIRT1) gene polymorphisms in antituberculosis- drug-induced hepatotoxicity in a prospective cohort study.
abstract: OBJECTIVE
  Antituberculosisdrug-induced hepatotoxicity (ATDH) is a common and sometimes serious side effect related to tuberculosis (TB) treatment. A number of risk factors and host genetics contribute to the development of ATDH. However, genetic factors of ATDH remain to be identified. Silent Information Regulator 1 (SIRT1), an essential metabolism gene, was proved to be involved in ATDH in mice. The aim of this investigation was to study the association between ATDH and tag-single nucleotide polymorphisms (tag-SNPs) of the SIRT1 gene in a prospective cohort study in patients with TB.
  
  
  METHODS
  280 newly diagnosed TB patients were recruited in this study before starting first line anti-TB treatment and were followed up for 3 months after initiating anti-TB therapy. The tag-SNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese Beijing. Genotyping was performed by polymerase chain reaction (PCR) and the Sequenom MassARRAY iPLEX platform.
  
  
  RESULTS
  24 (9.8%) of the 245 patients included in the final analysis developed hepatotoxicity during the following up period. No significant differences in the allele, genotype, or haplotype frequency distributions of the tag- SNPs (rs7069102, rs2273773, rs4746720) of the SIRT1 gene were identified between the ATDH and non-ATDH groups (all p > 0.05).
  
  
  CONCLUSIONS
  The SIRT1 gene may not contribute to the risk for developing hepatotoxicity during anti-TB treatment in the Han Chinese population.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Yan
authors.forename: Jing-Can
authors.initials: JC
authors.lastname: Wu
authors.forename: Gui-Yi
authors.initials: GY
authors.lastname: Ji
authors.forename: Shou-Quan
authors.initials: SQ
authors.lastname: Wu
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Huang
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: He
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D044466:Asian People; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D056564:Sirtuin 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; C447939:SIRT1 protein, human; D056564:Sirtuin 1