N-Acetyltransferase 2 (NAT 2) Genotyping
Test Code
NAT 2
CPT Codes
83891 x1; 83892 x2; 83900 x1; 83901 x3; 83914 x7; 83909 x1; 83912 x1; 83912-25 x1
Specimen
Whole blood or buccal swabs
Volume
5 mL of whole blood or four buccal swabs
Minimum Volume
3 mL of whole blood or four buccal swabs
Container
Lavender-stopper (EDTA) tube or paper envelope for dried buccal swabs
Storage Instructions
Maintain at room temperature or refrigerate
Cause for Rejection
Hemolyzed specimen; quantity not sufficient
Use
N-Acetyltransferase 2 (NAT2) catalyzes the activation and/or deactivation of a variety of aromatic amine drugs and carcinogens. Substrates include isoniazod, procainamide, hydralazine, and nitrazepam. Detecting variants of the NAT2 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of NAT2 substrates. The assay detects the 7 most frequent single nucleotide polymorphisms of the NAT2 gene: 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, 803A>G, and 857G>A.
.Limitations
Other variants of the NAT2 gene that are not detected in this assay may influence drug metabolism. NAT2 metabolic capacity is also influenced by concomitant medications, inhibitors, inducers, diet, environmental agents, and various disease states. All factors should be considered as part of the overall patient management strategy.
Methodology
Polymerase chain reaction-allele specific primer extension (FlexMAP system on Luminex instrument).
Turnaround Time
Five business days after receipt of specimen. STAT turnaround time of 3 business days is available for an additional charge.
References
http://www.louisville.edu/medschool/pharmacology/NAT2.html
Zhu, et al. Simultaneous determination of seven N-acetyltransferase-2 polymorphisms by allele-specific primer extension assay. Clin Chem 2006;52(6):1033-9.
Tanaka, et al. Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene. J Rheumatol. 2002 Dec;29(12):2492-9.
Blum, et al. Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression. DNA Cell Biol. 1990 Apr;9(3):193-203.
Bell, et al. Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans. Carcinogenesis. 1993 Aug;14(8):1689-92.
Deguchi, et al. Correlation between acetylator phenotypes and genotypes of polymorphic arylamine N-acetyltransferase in human liver. J Biol Chem. 1990 Aug 5;265(22):12757-60.
Vatsis, et al. Diverse point mutations in the human gene for polymorphic N-acetyltransferase. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6333-7.
Blum,et al. Molecular mechanism of slow acetylation of drugs and carcinogens in humans. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5237-41.
Hickman, et al. N-acetyltransferase polymorphism. Comparison of phenotype and genotype in humans. Biochem Pharmacol. 1991 Aug 8;42(5):1007-14.
Cascorbi, et al. Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. Am J Hum Genet. 1995 Sep;57(3):581-92.
Gross, et al. Distribution of concordance of N-acetyltransferase genotype and phenotype in an American population. Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):683-92.