Association of NAT2 Polymorphisms with Type 2 Diabetes in a Population from Bosnia and Herzegovina

Background and Aims. 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% Cl = 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% Cl = 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. (C) 2011 IMSS. Published by Elsevier Inc.