title: Association of NAT2 polymorphisms with type 2 diabetes in a population from Bosnia and Herzegovina.
abstract: OBJECTIVE
  N-acetyltransferase 2 (NAT2) is a drug-metabolizing enzyme, which is genetically variable in human populations. Polymorphisms in the NAT2 gene have been associated with drug efficacy and toxicity as well as disease susceptibility. Recently, an association of NAT2 gene variation with risk of type 2 diabetes mellitus (T2DM) has been suggested. This is the first study performed in a population from Bosnia and Herzegovina (BH) in which the frequency of two common NAT2 polymorphisms, 341T>C (NAT2*5) and 590G>A (NAT2*6) was determined in diabetic patients.
  
  
  METHODS
  The frequency of the NAT2*5 (341T>C) and NAT2*6 (590G>A) polymorphisms was analyzed by employing TaqMan SNP Genotyping Assays (Applied Biosystems) in a group of 63 patients with T2DM and 79 nondiabetic subjects.
  
  
  RESULTS
  Our data demonstrated that the frequencies of NAT2*5 (341T>C) and NAT2*6 (590G>A) polymorphisms in BH population were in line with the Caucasians genotype data. The NAT2*5 and NAT2*6 alleles were in high linkage disequilibrium (D' = 0.969). Strinkingly, there was a significant difference in genotype frequencies for NAT2*5 (p <0.05) and NAT2*6 (p <0.001) polymorphisms between diabetic and nondiabetic subjects. NAT2*5 polymorphism was associated with 2.4-fold increased risk for developing T2DM (adjusted OR = 2.40, 95% CI = 1.10-5.25, p = 0.028). On the contrary, NAT2*6 variant significantly decreased by 5-fold susceptibility to the disease (adjusted OR = 0.20, 95% CI = 0.09-0.43, p <0.001).
  
  
  CONCLUSIONS
  Our data demonstrated that NAT2 genetic variation appeared to be an important risk factor in development of T2DM.
authors.affiliation: Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Bosnia and Herzegovina. sabinasemiz@hotmail.com
authors.forename: Sabina
authors.initials: S
authors.lastname: Semiz
authors.forename: Tanja
authors.initials: T
authors.lastname: Dujic
authors.forename: Barbara
authors.initials: B
authors.lastname: Ostanek
authors.forename: Zelija
authors.initials: Z
authors.lastname: Velija-Asimi
authors.forename: Besim
authors.initials: B
authors.lastname: Prnjavorac
authors.forename: Tamer
authors.initials: T
authors.lastname: Bego
authors.forename: Maja
authors.initials: M
authors.lastname: Malenica
authors.forename: Barbara
authors.initials: B
authors.lastname: Mlinar
authors.forename: Becir
authors.initials: B
authors.lastname: Heljic
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
authors.forename: Adlija
authors.initials: A
authors.lastname: Causevic
mesh_terms: D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D017522:Bosnia and Herzegovina; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human