Should ugt1a1 genotyping be used to predict response to. It helps investigate the cause of jaundice and detect bilirubin metabolism disorders molecular testing, in general, can be performed using a variety of methods. The gene view histogram is a graphical view of mutations across ugt1a1. A common dinucleotide repeat polymorphism in the ugt1a1 promoter region ugt1a1 28 has been correlated with toxicity in cancer patients receiving irinotecancontaining therapy. Udp glucuronosyltransferase 1 family, polypeptide a1. Impact of ugt1a1 gene polymorphisms on plasma dolutegravir trough concentrations and neuropsychiatric adverse events in japanese individuals infected with hiv1 hiroki yagura1, dai watanabe2. This gene is part of a complex locus that encodes several udpglucuronosyltransferases. Click on a disease name to see all genes associated with that disease. Snapback primer genotyping of the gilbert syndrome ugt1a1. The disease is caused by mutations in the ugt1a1 gene, which result in the. The ugt1a1 28 change, however, is uncommon in asian populations.
Asians with gilbert syndrome often have a mutation in one copy of the ugt1a1 gene that results in the change of a single protein. This test can be completed in approximately 2 hours from isolation of dna to test result. Irinotecan is metabolized by a gene called ugt1a1 in the liver. An in silico analysis was performed on the polymorphic markers in the ugt1a1 gene region, which were reported in databases dbsnp, alfred, ucsc genome browser, snpper and opensnp. Ugt1a1 gene mutations cause accumulation of sn38, which may lead to irinotecanrelated toxicities neutropenia, diarrhea. Ugt1a1 analysis will also detect the ugt1a1 28 variant in the promoter region of the ugt1a1 gene, if present.
Multivariate analysis revealed that carrying one or two ugt1a1 6 gene polymorphisms, one ugt1a1. Pfam database, swissmodel, and pymol were used for ugt1a1 protein domain analysis and protein modeling for assessing the effect of novel missense variants on. Highresolution instrumentation and targeted software for data analysis are required to generate reproducible melting curves 33. Analysis of genetic variation of rs4148326 marker located in.
The 6 and 28 heterozygous patients also showed significantly higher values than those shown by patients with the normal allele. Racial variability in the udpglucuronosyltransferase 1. Amplification of regions of the ugt1a1 gene using allelespecific probes. Irinotecan is metabolized to form active sn38, which is further conjugated and detoxified by udpglucuronosyltransferase ugt 1a1 enzyme. The kit contains primers and reagents for amplification of the genes, plus buffers.
Clinical significance of ugt1a1 gene polymorphisms on. These mutations are displayed at the amino acid level across the full length of the gene by default. This gene encodes a udpglucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into watersoluble, excretable metabolites. Sequence analysis of the patients ugt1a1 gene revealed a.
Ugt1a1 genetic variations and a haplotype associated with. Lengths of the ta repeat polymorphism in the promoter region of the utg1a1 gene are determined by fragment analysis. Plus analysis increases the likelihood of finding a genetic diagnosis for your patient, as large deletions and duplications cannot be detected using sequence analysis alone. Udpglucuronosyltransferase 11 also known as ugt1a is an enzyme that in humans is encoded by the ugt1a1 gene ugt1a is a uridine diphosphate glucuronosyltransferase udp. Ugt1a1 gene mutations and neonatal hyperbilirubinemia in.
Common and rare variants of ugt1a1 have been known to contribute to nh etiology. The allele frequency and population status of the alleles were estimated using genepop, fbat, powermarker and arlequin software. Neonatal hyperbilirubinemia nh is a common finding in newborn babies in indonesia. If arup consult does not answer your test selection and interpretation questions, or if youd like to suggest ways to improve content or usability, please leave a message for the arup clinical content team. Pdf comprehensive analysis of ugt1a1 polymorphisms through. Haplotype structure of the udpglucuronosyltransferase 1a1. The aim of this study was to analyze if ugt1a1 tan promoter variants can. The alleles detected include the common normal allele 1 with 6 ta repeats and the common abnormal allele 28 7.
Certain changes in a gene known as ugt1a1 have been found to affect how quickly a persons body metabolizes changes irinotecan from its active to inactive form. Ugt1a1 gene analysis common variants ui health care. Ugt1a1 gene is responsible for glucuronidation of the active metabolite of irinotecan. The ugt1a1 pyro kit is used for genotyping of allele variant 28 and allele variant 6 of the human ugt1a1 gene. Gilbert and criglernajjar syndrome ugt1a1 gene sequencing. Logistic regression analysis showed odds ratios or of 2. Analysis of the ugt1a1 genotype in hyperbilirubinemia patients. This study evaluated the ugt1a1 genotypes in hyperbilirubinemia patients from southeastern china. Variations in ta repeat number in the tataaa element of the 5 ugt1a1. Which is the best free gene expression analysis software. This study aimed to investigate whether ugt1a1 gene mutation is associated with. I need to perform analysis on microarray data for gene expression and signalling pathway identification. Densitometric analysis was performed using the volume analysis tool of imagelab software biorad laboratories inc. Interpretation of dna analysis the active form of irinotecan, an antineoplastic agent, is deactivated by glucuronidation action of the ugt1a1 enzyme.
Ugt1a1 gene analysis coding and billing guidelines cm00074. Analysis of the ugt1a1 genotype in hyperbilirubinemia. Ugt1a1 genotyping for gilbert syndrome tests gtr ncbi. Association of ugt1a128 polymorphisms with irinotecan. Therefore, ugt1a1 gene analysis services are statutorily excluded tests. Gtr test id help each test is a specific, orderable test from a particular laboratory, and is assigned a unique gtr accession number. Blueprint genetics ugt1a1 single gene test ugt1a1 single gene test. To ensure accuracy of ugt1a1 ta n rs3064744 genotyping for use in pharmacogenomicsbased irinotecan dosing, we tested the concordance of several commonly used genotyping technologies.
Statistical analysis of the results was performed using the genepop software. The moldx team has determined ugt1a1 gene analysis has insufficient evidence to support the required clinical utility for the established medicare benefit category. The ugt1a1 mutation analysis test is used to detect abnormalities in the ugt1a1 gene. Nevertheless, to the best of our knowledge, this is one of the first studies to analyze the haplotype structure of the ugt1a1 gene including both promoter and coding regions and to assess the haplotypephenotype correlation between the ugt1a1 gene. The ugt1a1 gene is part of a gene complex located on chromosome 2 that encodes several enzymes called uridine diphosphate udpglycuronosyl transferases. Genetic diagnosis and pathogenic analysis of an atypical hereditary. Clinical test for gilberts syndrome offered by genetic services laboratory. Ugt1a1 genotypes and unconjugated hyperbilirubinemia. Primers used for hrm analysis of ugt1a1 gene mutations. The most prevalent ugt1a1 gene polymorphism is the insertion mutation in caucasians, which. Variants in ugt1a1 cause criglernajjar syndrome cn, types i and ii. Clinical significance of ugt1a1 gene polymorphisms on irinotecanbased regimens as the treatment in metastatic colorectal cancer minmin li,1 zhehai wang,2 jun guo,2 jie liu,2.
This study evaluated the ugt1a1 genotypes in hyperbilirubinemia patients from. The biofilmchip microarray consists of a polyester film coated with proprietary multilayer components designed for dna analysis. If analysis of only the ugt1a1 promoter ta repeat region 28, 36, 37 alleles is desired, see u1a1v udpglucuronosyl transferase 1a1 ta repeat genotype, ugt1a1. This variant, when present in the homozygous state, is associated with gilbert syndrome.
The locus includes thirteen unique alternate first exons followed by four common. Heuristic genotype groupings and principal component analysis demonstrated concordance for illumina sequencing, fragment analysis. We enrolled 60 patients from southeastern china 44 men and 16 women. These enzymes perform a chemical reaction called glucuronidation, in which a compound called glucuronic acid is attached conjugated to one of a number of different substances. The most common mutation in this population replaces the amino acid glycine with the amino acid. Criglernajjar syndrome testing ugt1a1 the university. Studies of patients treated with irinotecan have reported that major doselimiting toxicities are associated with polymorphisms in the tata box of the ugt1a1 gene. Ugt1a1 activity declines with the increased length of ta repeats beutler et al.
Ugt1a1 targeted mutation analysis 850 what are ugt1a1 and irinotecan definition irinotecan is a chemotherapy drug often prescribed together with other standard agents for treating patients with metastatic and recurrent colorectal cancer. Roles of ugt1a1 gly71arg and tata promoter polymorphisms. This change is associated with reduced expression of the ugt1a1 gene and. Genotyping analysis was performed by fragment size analysis for ugt1a1 28, direct sequencing for ugt1a73 and ugt1a922, and taqman assays for ugt1a1 93, ugt1a1 6, ugt1a1 27, ugt1a1. Clinvar and hgmd into our clinical interpretation software. Cn1 is the more severe form and is characterized by the total absence of hepatic ugt1a1 activity. These enzymes perform a chemical reaction called glucuronidation, a major pathway that enhances the elimination of small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into watersoluble metabolites that can. Predictive role of the ugt1a1, ugt1a7, and ugt1a9 genetic. Lengths of the ta repeat polymorphism in the promoter region of the utg1a1 gene are determined by fragment analysis using capillary electrophoresis. Irinotecan unexpectedly causes severe toxicity of leukopenia or diarrhea.
A polymorphism in the promoter of the udpglucuronosyltransferase 1 ugt1a1 gene has been shown to cause gilbert syndrome, a benign form of unconjugated bilirubinemia. Other polymorphism of ugt1a1, such as, ugt1a1 6, ugt1a1. Asians with gilbert syndrome often have a mutation in one copy of the ugt1a1 gene that results in the change of a single protein building block amino acid in the bilirubinugt enzyme. It helps investigate the cause of jaundice and detect bilirubin metabolism disorders molecular testing, in.