Test Catalog

Test Id : NAT2

N-Acetyltransferase 2 Gene (NAT2), Full Gene Sequence, Whole Blood

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

Identifying patients who may require isoniazid dosing adjustments

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
NAT2F NAT2, Full Gene Sequence No Yes
NAT2S NAT2, Gene Sequencing No Yes

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

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

Polymerase Chain Reaction (PCR) Followed by DNA Sequence 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, Full Gene Sequence

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

Arylamine N-acetyltransferase-2

Dapsone

Hydralazine

Isoniazid

NAT-2 (N-acetyltransferase 2 Gene)

Nitrazepam

Pronestyl (Procainamide)

Zonisamide (Zonegran)

N-acetyltransferase Type 2

Polymorphic Arylamine N-acetyltransferase (PNAT)

Arylamide Acetylase 2 (AAC2)

Specimen Type
Describes the specimen type validated for testing

Whole Blood EDTA

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

Multiple whole blood EDTA genotype tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.

 

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube.

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) form with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.3 mL

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

No specimen should be rejected.

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
Whole Blood EDTA Ambient (preferred)
Refrigerated

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

Identifying patients who may require isoniazid dosing adjustments

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. 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, 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, zonisamide, and isoniazid. 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.

 

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

859Del

I114T


K268R


S287 Frameshift

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

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

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.

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

Blood samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow 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 blood or marrow 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 NAT2 status.

 

This test sequences the entire NAT2 gene. All variants, including novel variants not listed, should be detected. However, novel variants not described in the literature may be of unknown significance.

 

Mutations in the primer binding regions can affect the testing and, ultimately, the genotyping interpretation made.

 

Drug-drug interactions and drug or metabolite inhibition must be considered when dealing with heterozygous individuals. Drug or metabolite inhibition can reduce residual functional NAT2 catalytic activity. Acetaminophen is a significant inhibitor of NAT2.

 

Patients may develop isoniazid toxicity problems if liver and kidney function are impaired, even in the absence of slow or intermediate acetylator status.

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

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

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

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

The entire NAT2 gene is amplified by PCR. The single amplicon is sequenced in 4 positions in both directions for a total of 8 sequences. These 8 sequencing reactions provide complete bidirectional sequencing coverage of NAT2.(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.

Varies

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.

7 to 12 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: 2 weeks Extracted DNA: 2 months

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

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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. This test 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

Test Id Test Order Name Order LOINC Value
NAT2 NAT2, Full Gene Sequence 90259-3
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

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