Sorted By Test Name - Mayo Medical Laboratories

NAT2O
60345
hepatitis, peripheral neuropathy, and sideroblastic anemia, are associated more often with a slow NAT2
acetylator phenotype. These individuals may require a lower dose to avoid adverse reactions. The NAT2
gene contains a single intronless exon of 870 base pairs and encodes 290 amino acids. NAT2 is highly
polymorphic and contains 16 known single nucleotide polymorphisms (SNPs) and 1 single base pair
deletion. These polymorphisms are combined into 36 known haplotype alleles. Each individual haplotype
is predictive of either a fast or slow acetylator phenotype. Individuals with 2 fast haplotypes are predicted
to be extensive (normal) metabolizers, while those with 1 fast and 1 slow haplotype are intermediate
metabolizers, and those with 2 slow haplotypes are poor metabolizers.(2,3) Studies with patients who
have different acetylator haplotypes have correlated the ratio of plasma N-acetylisoniazid/isoniazid drug
concentrations with haplotypes, with slow and intermediate acetylators having lower ratios than fast
acetylators.(4) NAT2 Allele Nucleotide Change Amino Acid Change Predicted Acetylator Phenotype *4
None None Fast *5A 341T->C 481C->T I114T Slow *5B 341T->C 481C->T 803A->G I114T K268R
Slow *5C 341T->C 803A->G I114T K268R Slow *5D 341T->C I114T Slow *5E 341T->C 590G->A
I114T R197Q Slow *5F 341T->C 481C->T 759C->T 803A->G I114T K268R Slow *5G 282C->T
341T->C 481C->T 803A->G I114T K268R Slow *5H 341T->C 481C->T 803A->G 859T->C I114T
K268R I287T Slow *5I 341T->C 411A->T 481C->T 803A->G I114T L137F K268R Slow *5J 282C->T
341T->C 590G->A I114T R197Q Slow *6A 282C->T 590G->A R197Q Slow *6B 590G->A R197Q
Slow *6C 282C->T 590G->A 803A->G R197Q K268R Slow *6D 111T->C 282C->T 590G->A R197Q
Slow *6E 481C->T 590G->A R197Q Slow *7A 857G->A G286E Slow *7B 282C->T 857G->A G286E
Slow *10 499G->A E167K Undetermined *11A 481C->T None Undetermined *11B 481C->T 859Del
S287 Frameshift Undetermined *12A 803A->G K268R Fast *12B 282C->T 803A->G K268R Fast *12C
481C->T 803A->G K268R Fast *12D 364G->A 803A->G D122N K268R Undetermined *13 282C->T
None Fast *14A 191G->A R64Q Slow *14B 191G->A 282C->T R64Q Slow *14C 191G->A 341T->C
481C->T 803A->G R64Q I114T K268R Slow *14D 191G->A 282C->T 590G->A R64Q R197Q Slow
*14E 191G->A 803A->G R64Q K268R Slow *14F 191G->A 341T->C 803A->G R64Q I114T K268R
Slow *14G 191G->A 282C->T 803A->G R64Q K268R Slow *17 434A->C Q145P Undetermined *18
845A->C K282T Undetermined *19 190C->T R64W Undetermined
Useful For: Identifying patients who may require isoniazid dosing adjustments
Interpretation: The wild-type (normal) genotype for NAT2 is *4. This is the most commonly
occurring allele in some, but not all, ethnic groups.(5) Individuals are classified as being slow,
intermediate, or fast acetylators depending on their diplotypes. Slow acetylators have 2 slow haplotypes,
fast acetylators have 2 fast haplotypes, and intermediate acetylators have 1 of each. Slow acetylators
receiving isoniazid therapy should be monitored for signs of toxicity. Dose reductions may be considered
for both slow and intermediate acetylators. However, it should be verified that the reduced isoniazid dose
produces serum levels within the therapeutic range.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Meyer U: Polymorphism of human acetyltransferases. Environ Health
Perspect 1994;102:213-216 2. Sabbagh A, Darlu P: Inferring haplotypes at the NAT2 locus: the
computational approach. BMC Genetics 2005;6:30 3. Leff M, Fretland A, Doll M, and Heins D: Novel
human N-acetyltransferase 2 alleles that differ in mechanism for slow acetylator phenotype. J Biol Chem
1999;274:34519-34522 4. Chen B, Li J-H, Xu Y-M, et al: The influence of NAT2 genotypes on the
plasma concentration of isoniazid and acetylisoniazid in Chinese pulmonary tuberculosis patients. Clin
Chim Acta 2006;365:104-108 5. Lin H, Han C, Lin B, Hardy S: Ethnic distribution of slow acetylator
mutations in the polymorphic N-acetyltransferase (NAT2) gene. Pharmacogenetics 1994;4:125-134
N-Acetyltransferase 2 Gene (NAT2), Full Gene Sequence, Saliva
Clinical Information: Arylamine N-acetyltransferase type 2 (NAT2) is a highly polymorphic phase 2
metabolic enzyme that conjugates hydrazine derivatives and aromatic amine drugs with acetyl-groups.
NAT2 also is involved in the acetylation and activation of some procarcinogens.(1) Individuals acetylate
drugs at different rates by NAT2, and are described as having slow, intermediate, or fast acetylator
phenotypes. A gradient exists in which the prevalence of slow acetylator phenotypes increases with
decreasing distance to the equator. Near the equator, up to 80% of individuals may be slow acetylators,
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