Interleukin 28B (IL28B) Polymorphism (rs12979860), Saliva
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Predicting responsiveness of genotype 1 hepatitis C viral infections to combined pegylated-interferon and ribavirin-based therapies
This saliva-based test is especially useful for establishing the IL28B genotype in patients who received a heterologous blood transfusion, in the preceding 45 days (6 weeks) or allogeneic bone marrow transplants.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) Followed by 5'-Nuclease End-Point Allelic Discrimination Analysis
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
IL28B Polymorphism Genotype, Saliva
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
When this test is ordered, DNA extraction will always be performed at an additional charge. However, for multiple saliva genotype test orders, only a single specimen is needed. The DNA extraction will only be charged once.
Container/Tube: Oragene DNA Self-Collection Kit (Supply T651)
Specimen Volume: Full tube
1. Fill tube to line.
2. Send specimen in original container per kit instructions.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Individuals with hepatitis C virus (HCV) genotype 1 infections have variable responses to treatment with pegylated-interferon and ribavirin combination therapy. Some individuals will respond to treatment with sustained viral response, while other patients have poor response and fail to achieve sustained viral clearance.
Response to pegylated-interferon and ribavirin combination therapy in HCV genotype 1-infected individuals has been found to be closely associated with a single-nucleotide polymorphism (SNP), designated rs12979860, located 3 kilobases upstream from the interleukin 28B gene locus (IL28B) present on human chromosome 19.
HCV genotype 1-infected individuals with the CC genotype, as compared to either the CT or TT genotypes, of this SNP in IL28B have approximately 2- to 3-fold greater rates of sustained viral response to combined pegylated-interferon and ribavirin therapy.(1) Similar increases in sustained viral response rates were observed across various racial groups, including European Americans (95% CI, 1.8- to 2.3-fold), African Americans (95% CI, 1.9- to 4.7-fold), and Hispanics (95% CI, 1.4- to 3.2-fold).(1) The CC genotype has also been associated with a 3-fold increase in rate of spontaneous clearance of HCV.(2) The SNP in IL28B is only one of many factors that can influence response rates to pegylated-interferon and ribavirin combination therapy in HCV genotype 1 infection, and the SNP genotype result should be interpreted in the context of other clinical factors present in a given patient.
Frequency of the rs12979860 C allele varies across different racial and ethnic groups. The rs12979860 C variant is most frequently present in individuals from East Asia (allele frequency >0.9) and least common in individuals of African origin (allele frequency 0.2-0.5).(2) In a recent US-based study, the favorable CC genotype was observed in 37% of Caucasians, 29% Hispanics, and 14% of African Americans tested.
The mechanism by which the IL28B genotype mediates response to pegylated-interferon and ribavirin combination therapy among HCV genotype 1-infected individuals is not yet understood and is the subject of intense ongoing research. The impact of the IL28B-related polymorphism on response rates in patients infected with HCV genotypes other than genotype 1 is still being investigated.
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 individual with IL28B-related rs12979860 CC genotype (ie, 2 copies of the C allele for the rs12979860 single-nucleotide polymorphism) responds more to pegylated-interferon and ribavirin combination therapy. Patients with CC genotype also show more spontaneous clearance of hepatitis C virus infection.
An individual carrying the IL28B-related rs12979860 CT genotype is less likely to respond to pegylated-interferon and ribavirin combination therapy.
An individual carrying the IL28B-related rs12979860 TT genotype is less likely to respond to pegylated-interferon and ribavirin combination therapy.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test does not detect polymorphism or mutations other than the single-nucleotide polymorphism of rs12979860 CT.
Drug-drug interactions and drug-metabolite inhibition must be considered.
Saliva specimen type should be used for patients who received a heterologous blood transfusion in the preceding 45 days (6 weeks), and for patients who have received an allogeneic bone marrow transplant.
IL28B is expressed in the liver following hepatitis C virus infection. For liver transplant patients, the IL28B genotype of the recipient and the donor are independent predictors of sustained virologic response with combined pegylated-interferon and ribavirin therapy.(4)
Rare polymorphisms exist and could lead to false-negative or false-positive results.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Ge D, Fellay J, Thompson AJ, et al: Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399-401
2. Thomas DL, Thio CL, Martin MP, et al: Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 2009;461:798-801
3. Thompson AJ, Muir AJ, Sulkowski MS, et al: Interleukin-28B polymorphism improves viral kinetics and is the strongest pre-treatment predictor of sustained virologic response in hepatitis C virus-1 patients. Gastroenterology 2010;139:120-129
4. Chalton MR, Thompson A, Veldt BJ, et al: Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection. Hepatology 2011;53:317-324
Method Description Describes how the test is performed and provides a method-specific reference
Real-time PCR with allele-specific probes is used to detect a single-nucleotide polymorphism (SNP) (rs12979860 CT) on chromosome 19q13. The rs12979860 SNP maps 3 kilobases upstream of the IL28B gene (OMIM: 607402) which encodes the type III interferon IFN-Lambda 3. No other polymorphisms are detected by this assay. Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur. Specimens producing unusual results, or results not consistent with patient outcome, may be evaluated by bidirectional DNA sequencing.(Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday, Wednesday, Friday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81400-IL28B (interleukin 28B [interferon, lambda 3]) (eg, drug response), rs12979860 variant
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|34630||IL28B Polymorphism Genotype||In Process|
|34631||IL28B Interpretation||In Process|