Inosine Triphosphatase (ITPA) and Interleukin 28 B (IL28B)-Associated Variants, 4 SNPs
2006344
 
Ordering Recommendation
Detect genetic variants associated with interleukin 28 B (IL28B) and inosine triphosphatase (ITPA) that may aid in predicting probability of therapeutic response (IL28B) and dose planning (ITPA).
Mnemonic
ITPA-IL28B
Methodology
Polymerase Chain Reaction/Single Nucleotide Extensions
Performed
varies
Reported
7-10 days
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory.
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).  
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL)  
Storage/Transport Temperature
Refrigerated.  
Unacceptable Conditions
 
Remarks
 
Stability
Ambient: 3 days; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
By report
Interpretive Data
Background Information for Inosine Triphosphatase (ITPA) and Interleukin 28 B (IL28B)-Associated Variants, 4 SNPs
Characteristics:
Hepatitis C is a disease caused by infection with hepatitis C virus (HCV). It can result in cirrhosis, liver failure and hepatocellular carcinoma in chronically infected individuals. HCV is categorized into six genotypes. HCV genotype 1 (HCV-1) accounts for 75 percent of U.S. cases. Therapy for chronic infection consists of peginterferon and ribavirin combination therapy, and more recently protease inhibitors. Combination peginterferon/ribavirin therapy is effective in eliminating HCV RNA in 40-50 percent of individuals with HCV-1. Single nucleotide polymorphisms (SNP) rs12979860 C/T and SNP rs8099917 T/G, located upstream of the IL28B gene, encoding for lambda or type III interferons, have been associated with both spontaneous clearance and response to peginterferon/ribavirin therapy in individuals infected with HCV-1. For SNP rs12979860, the CC genotype is associated with a 2-3 fold greater rate of sustained virological response (SVR) following peginterferon/ribavirin therapy, while the CT and TT genotypes are less likely to respond to treatment. For SNP rs8099917, the TT genotype is associated with a higher rate of SVR after peginterferon/ribavirin therapy, while the TG and GG genotypes are less likely to respond to treatment and achieve SVR. Two additional SNPs, rs1127354 A/C and rs7270101 C/A, within the inosine triphosphatase (ITPA) gene are associated with decreased ITPase activity and protection against RBV treatment-related anemia in patients with HCV infection. For SNP rs1127354, the AA or AC genotypes are protective while the CC genotype is associated with susceptibility to RBV-induced hemolytic anemia. For SNP rs7270101, the CC or CA genotypes are protective while the AA genotype is associated with susceptibility to RBV-induced hemolytic anemia.
Prevalence:
4.1 million Americans (1.6 percent of the U.S. population) have anti-HCV antibodies.

Allele Frequency:


Assoc. Gene SNP Favorable African Asian Caucasian Hispanic
allele American

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IL28B
rs12979860 0.50 0.90 0.75 0.70
C allele
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rs8099917 Unk. 0.88 0.75 Unk.
T allele
------------------------------------------------------------------------------------------------------------------------
ITPA
rs1127354 0.04 0.15 0.07 0.06
A allele
--------------------------------------------------------------------------------------------------------
rs7270101 0.09 Rare 0.11 0.07
C allele

Variants Tested:
SNPs rs12979860 C/T and rs8099917 T/G near IL28B; SNPs rs1127354 A/C and rs7270101C/A in ITPA.
Clinical Sensitivity:
Unknown.
Methodology:
Multiplex PCR and single nucleotide extension (SNE) and capillary electrophoresis.
Analytical Sensitivity & Specificity:
99 percent.
Limitations:
SNPs other than those targeted will not be detected. Mutations in other genes and non-genetic factors that may affect response to hepatitis C therapy are not detected. For HCV genotypes other than type 1, the usefulness of these SNPs for predicting response to therapy is unknown. Diagnostic errors can occur due to rare sequence variations.



Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

See Compliance Statement C: www.aruplab.com/CS
Note
CPT Code(s)
81479 (2)
Components
Component Test Code*Component Chart Name
2006345ITPA and IL28B-Assoc Var, 4 SNPs Spec
2006346ITPA rs1127354 Genotype
2006347ITPA rs7270101 Genotype
2006348IL28B rs12979860 Genotype
2006349IL28B rs8099917 Genotype
2006350ITPA-IL28B Interpretation
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, contact interface support at interface.support@aruplab.com.
Cross References