Test Catalog

Test Id : NAT2Q

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N-Acetyltransferase 2 (NAT2) Genotype, Varies

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying patients who may be at risk for altered metabolism of drugs that are substrates of arylamine N-acetyltransferase type 2 (NAT2), including isoniazid

Method Name
A short description of the method used to perform the test

Real-Time Polymerase Chain Reaction (PCR) with Allelic Discrimination Analysis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

NAT2 Genotype, V

Aliases
Lists additional common names for a test, as an aid in searching

Amifampridine

Arylamide Acetylase 2 (AAC2)

Arylamine N-acetyltransferase-2

Dapsone

Hydralazine

Isoniazid

N-acetyltransferase Type 2

NAT-2 (N-acetyltransferase 2 Gene)

Nitrazepam

Procainamide

Sulfasalazine

Tuberculosis

Specimen Type
Describes the specimen type validated for testing

Varies

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Genotype Test List for a list of tests that can be ordered together.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

 

Specimen Type: Extracted DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 50 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send 1 of the following with the specimen:

-Neurology Specialty Testing Client Test Request (T732)

-Therapeutics Test Request (T831)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

Blood: 0.4 mL

Saliva: 1 swab

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying patients who may be at risk for altered metabolism of drugs that are substrates of arylamine N-acetyltransferase type 2 (NAT2), including isoniazid

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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.(1) NAT2 also is involved in the acetylation and activation of some procarcinogens.(1,2)

 

Individuals acetylate drugs at different rates by NAT2 and are described as having slow, intermediate, or rapid (fast) acetylator phenotypes. Some studies, which have examined diversity of NAT2 haplotypes among individuals of different ethnicities hypothesize that the NAT2 slow acetylator phenotype was positively selected for in the transition from hunter-gatherer or nomadic lifestyle to an agricultural or pastoral lifestyle.(3) 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, while in some more northern countries, as few as 10% of the population may have the slow acetylator phenotype.

 

A number of drugs are metabolized by NAT2 including procainamide, dapsone, nitrazepam, hydralazine, sulfasalazine, amifampridine, and isoniazid.(4) Isoniazid is used to treat and prevent tuberculosis and is still used as a primary treatment agent. Adverse reactions with isoniazid, which include nausea, drug-induced 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.(4) Of note, acetaminophen is a significant NAT2 inhibitor.

 

The NAT2 gene contains a single intronless exon of 870 base pairs and encodes 290 amino acids. NAT2 is highly polymorphic and contains at least 16 known single nucleotide variants and 1 single base pair deletion. These genetic variants are combined into 36 known haplotypes or alleles. Each individual haplotype is predictive of either a rapid (fast) or slow acetylator phenotype. Individuals with 2 rapid haplotypes are predicted to be rapid (normal) metabolizers, while those with 1 rapid and 1 slow haplotype are intermediate metabolizers, and those with 2 slow haplotypes are poor metabolizers.(5,6) 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 rapid acetylators.(7)

 

NAT2 genotype results are used to predict metabolizer phenotypes, as indicated in the Table. Note that the reference allele for NAT2 is *4. If no variants are detected, the default genotype and phenotype reported are *4/*4 and rapid acetylator phenotype, respectively.

 

Table.

NAT2 allele

Predicted acetylator phenotype

*4

Rapid (normal)

*5

Slow

*6

Slow

*7

Slow

*10

Slow, but may be substrate dependent

*12D

Slow

*14

Slow

*17

Slow

*19

Slow

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided. The wild-type (normal) genotype for NAT2 is *4. This is the most commonly occurring allele in some, but not all, ethnic groups.(8)

 

Individuals are classified as being slow, intermediate, or rapid (fast) acetylators depending on their diplotypes. Slow acetylators have 2 slow haplotypes, rapid acetylators have 2 rapid (fast, normal) haplotypes, and intermediate acetylators have one of each.

 

The genotype, with associated star alleles, is assigned using standard allelic nomenclature as described by the Human NAT2 Alleles (Haplotypes) Database (http://nat.mbg.duth.gr/Human%20NAT2%20alleles_2013.htm).

 

For additional information regarding pharmacogenomic genes and their associated drugs, see Pharmacogenomic Associations Tables. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

 

Drug-drug interactions and drug-metabolite inhibition must be considered when adjusting medication dosage. It is important to interpret the results of testing and dose adjustments in the context of hepatic and renal function and patient age. For applicable medications, therapeutic drug monitoring is useful to verify that the drug concentration is within the therapeutic range.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Rare variants (ie, polymorphisms) may be present that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings (phenotype), additional testing should be considered.

 

Samples may contain donor DNA if obtained from patients who received nonleukoreduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell transplantation, a pretransplant DNA specimen is recommended for testing.

 

NAT2 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's arylamine N-acetyltransferase type 2 (NAT2) status.

 

This method may not detect all variants that result in altered NAT2 activity. Therefore, absence of a detectable variant does not rule out the possibility that a patient has altered NAT2 metabolism due to other NAT2 variants that cannot be detected with this method. Furthermore, when 2 or more variants are identified, the cis-/trans-status (whether the variants are on the same or opposite chromosomes) is often not known; therefore, multiple haplotypes may be provided.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Salazar-Gonzalez RA, Doll MA, Hein DW: Human arylamine N-acetyltransferase 2 genotype-dependent protein expression in cryopreserved human hepatocytes. Sci Rep. 2020 May 5;10(1):7566

2. Meyer UA: Polymorphism of human acetyltransferases. Environ Health Perspect. 1994 Oct;102 Suppl 6(Suppl 6):213-216

3. McDonagh EM, Boukouvala S, Aklillu E, Hein DW, Altman RB, Klein TE: PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2. Pharmacogenetics and Genomics. 2014 Aug;24(8):409-425

4. Hein DW, Millner LM: Arylamine N-acetyltransferase acetylation polymorphisms: paradigm for pharmacogenomic-guided therapy- a focused review. Expert Opin Drug Metab Toxicol. 2021 Jan;17(1):9-21

5. Sabbagh A, Darlu P: Inferring haplotypes at the NAT2 locus: the computational approach. BMC Genet. 2005 Jun 2;6:30

6. Leff MA, Fretland AJ, Doll MA, Hein DW: Novel human N-acetyltransferase 2 alleles that differ in mechanism for slow acetylator phenotype. J Biol Chem. 1999 Dec 3;274(49):34519-34522

7. Chen B, Li JH, Xu YM, Wang J, Cao XM: The influence of NAT2 genotypes on the plasma concentration of isoniazid and acetylisoniazid in Chinese pulmonary tuberculosis patients. Clin Chim Acta. 2006 Mar;365(1):104-108

8. Lin HJ, Han CY, Lin BK, Hardy S: Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene. Pharmacogenetics. 1994 Jun;4(3):125-134

Method Description
Describes how the test is performed and provides a method-specific reference

Genomic DNA is extracted from whole blood or saliva. Genotyping for NAT2 alleles is performed using a polymerase chain reaction (PCR)-based 5'-nuclease assay. Fluorescently labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the variant. If the detection probe is an exact match to the target DNA, the 5'-nuclease polymerase degrades the probe, the reporter dye is released from the effects of the quencher dye, and a fluorescent signal is detected. Genotypes are assigned based on the allele-specific fluorescent signals that are detected.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 8 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood/Saliva swab: 2 weeks Extracted DNA: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees :
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81479-Unlisted molecular pathology procedure

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
NAT2Q NAT2 Genotype, V 101141-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
616425 NAT2 Genotype 101142-8
616426 NAT2 Phenotype 101143-6
616427 Interpretation 69047-9
616428 Additional Information 48767-8
616430 Method 85069-3
616429 Disclaimer 62364-5
616431 Reviewed By 18771-6

Test Setup Resources

Setup Files
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Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports