Reference Interval:
By report
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| 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
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ITPA rs1127354 0.04 0.15 0.07 0.06
A allele
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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. Rare diagnostic errors may occur due to primer site mutations.
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
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| CPT Code(s): |
81479 (2)
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