N-acetyltransferase 1 and 2 polymorphisms and risk of diabetes mellitus type 2 in a Saudi population

BACKGROUND AND OBJECTIVES: There have been inconsistent reports on N-acetyltransferase (NAT) gene polymorphism in type 2 diabetes mellitus (T2DM), and data is particularly limited in the Arab population. Therefore, the main objective of this study was to identify whether the genetic polymorphisms of NAT1 and NAT2 play a role in susceptibility to T2DM in the Saudi population. DESIGN AND SETTING: A population-based, prospective genetic association case-control study on a Saudi population. PATIENTS AND METHODS: Whole blood, anthropometric measurements and biochemistry data were collected from 369 Saudi individuals (186 T2DM patients and 183 healthy controls). DNA was isolated from the blood. Polymorphism of NAT1 and NAT2 SNPs [NAT2*7B, rs1041983(C>T); NAT2*7, rs1799931(G>A); NAT2*6A, rs1799930(G>A); NAT2*5A, rs1799929(C>T); and NAT1*11A, rs4986988(C>T)] were evaluated by allelic discrimination using real-time PCR. RESULTS: Subjects with T2DM had a significantly increased body mass index (BMI), waist circumference, systolic and diastolic blood pressure, glucose, triglycerides, and LDL-cholesterol compared with healthy controls (P<.05). The rs1799931(G>A) genotype was detected in the control population but not in the T2DM population (P<. 001). The wild type (G) allele frequency was higher in T2DM than controls (P=.038). The mutant allele (A) in rs1799931(G>A) had a protective effect for T2DM (OR 0.32, 95% CI 0.16-0.62; P=.001). Regression analysis showed that BMI, systolic BP and triglycerides are potential risk factors for T2DM. CONCLUSION: The genotypes as well as the individual alleles of rs1799931(G>A) differed significantly between the case and control populations. The variation in the data reported so far suggest that polymorphism of the NAT gene may vary among different geographical areas. Environmental or dietary factors may also contribute to disease manifestation.