Functional effects of single nucleotide polymorphisms in the coding region of human N-acetyltransferase 1

Genetic variants of human N -acetyltransferase 1 (NAT1) are associated with cancer and birth defects. N - and O -acetyltransferase catalytic activities, Michaelis–Menten kinetic constants ( K m and V max ) and steady-state expression levels of NAT1-specific mRNA and protein were determined for the reference NAT1*4 and variant human NAT1 haplotypes possessing single nucleotide polymorphisms (SNPs) in the open reading frame. Although none of the SNPs caused a significant effect on steady-state levels of NAT1-specific mRNA, C97T(R33stop), C190T(R64W), C559T (R187stop) and A752T(D251V) each reduced NAT1 protein level and/or N - and O -acetyltransferase catalytic activities to levels below detection. G560A(R187Q) substantially reduced NAT1 protein level and catalytic activities and increased substrate K m . The G445A(V149I), G459A(synonymous) and T640G(S214A) haplotype present in NAT1*11 significantly ( P