.

LPL - LPL-ROHINI (NATIONAL REFERENCE LAB)

SECTOR - 18, BLOCK -E ROHINI DELHI 110085

Name DUMMY N189 Collected 29/7/2020 1:59:00PM

Received 29/7/2020 3:51:13PM

Lab No. 153672449 Age: 35 Years Gender: Male Reported 31/7/2020 2:54:42PM

A/c Status P Ref By: UNKNOWN Report Status Final

TEST CONDUCTED UGT1A1 Gene Polymorphism (Nucleotide TA Repeat) #

(PCR, Fragment analysis)

RESULTS

TA Repeats UGT1A1 Genotype

7/7 UGT1A1*28/*28

Interpretation
---------------------------------------------------------------------------------------------
| Genotype Nomenclature | Number of TA repeats | Remarks |
|-----------------------|----------------------|----------------------------------------------|
| | | Patients who are homozygous for 6 TA repeats |
| UGT1A1*1/*1 | 6/6 | demonstrate full enzyme activity and are |
| | | associated with minimal toxicity with |
| | | standard Irinotecan dosage. |
|-----------------------|----------------------|----------------------------------------------|
| | | Patients with one 6 TA allele and one 7 TA |
| UGT1A1*1/*28 | 6/7 | allele (6/7 heterozygous) demonstrate reduced|
| | | glucuronidation activity, with about 12.5% |
| | | risk of neutopenia due to toxicity. |
|-----------------------|----------------------|----------------------------------------------|
| | | Patients with 2 alleles each with 7 TA repeat|
| | | (7/7 homozygous) demonstrate severely reduced|
| UGT1A1*28/*28 | 7/7 | glucuronidation activity, with about 50 % |
| | | risk of severe toxicity and significant risk |
| | | for grade 4 neutropenia or severe diarrhea |
| | | following Irinotecan treatment. |
|-----------------------|----------------------|----------------------------------------------|
| | | Patients with one 7 TA allele and one 8 TA |
| UGT1A1*28/*37 | 7/8 | allele (7/8 heterozygous) demonstrate reduced|
| | | transcription rate and a lower enzyme level. |
|-----------------------|----------------------|----------------------------------------------|
| | | Patient with (UGT1A1*37,deficien allele) |
| UGT1A1*37/*37 | 8/8 | demonstrate an increased number of TA repeats|
| | | associated with both a reduced transcription |
| | | rate a lower enzyme level. |
---------------------------------------------------------------------------------------------

Note
1. This assay detects the four TATA box polymorphisms [*36(TA5), *1(TA6), *28(TA7) and
*37(TA8)] in the promoter region of the UDP glucuronosyltransferase gene (UGT1A1).
2. This assay does not detect any other variant of this gene.
3. Presence of PCR inhibitors in the sample may prevent DNA amplification.
4. This is an in-house developed assay.

Comment
UGT1A1 polymorphism and Irinotecan therapy
Irinotecan is an anti-cancer agent that is used for the treatment of metastatic carcinoma of the colon or
rectum and may also be used for lung, brain, and breast tumors. Although it prolongs survival, it causes

PatientReportSCSuperPanel.FLOWCYTO_DYNAMIC_SC (Version: 6)

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LPL - LPL-ROHINI (NATIONAL REFERENCE LAB)

SECTOR - 18, BLOCK -E ROHINI DELHI 110085

Name DUMMY N189 Collected 29/7/2020 1:59:00PM

Received 29/7/2020 3:51:13PM

Lab No. 153672449 Age: 35 Years Gender: Male Reported 31/7/2020 2:54:42PM

A/c Status P Ref By: UNKNOWN Report Status Final

severe (grade 3-4) diarrhea and neutropenia in approximately 20-35% of patients .

UDP-glucuronosyltransferase (UGT1A1) is responsible for the clearance, by glucuronidation, of drugs
(e.g., Irinotecan) and endogenous substances (e.g., bilirubin). Variations of the TA repeat length in the
UGT1A1 promoter TATA element may lead to decreased gene expression and accumulation of toxic
metabolite SN-38. UGT1A1 genotyping test result will provide valuable information to physicians prior to
initiating or modifying treatment or supplementing treatment with additional drugs.

UGT1A1 and Gilbert’s syndrome (GS)

GS can be caused by a variety of genetic changes, but in Caucasian and African -American populations, it
is most commonly associated with the UGT1A1*28 allele. This polymorphism impairs proper transcription
of UGT1A1 gene, resulting in decreased transcriptional activity of UGT 1A1 by about 70%; and thus reduced
enzyme activity which leads to the hyperbilirubinemia characteristic of GS. The *28 polymorphism occurs
with a frequency of 26-31% in Caucasians and 42-56% of African-Americans. About 10-15% of these
populations are homozygous for the *28 allele, but only 5% actually develop UGT1A1-associated
hyperbilirubinemia.
UGT1A1 and Crigler-Najjar syndrome
Crigler-Najjar syndrome, type I is associated with mutation(s) that result in a complete absence of normal
UGT1A1 enzyme, which causes a severe hyperbilirubinemia with levels of total serum bilirubin from 20 to
45 mg/dL. Phenobarbital treatment does not help to lower bilirubin level, because it only increases the
amount of mutated UGT1A1 enzyme, which is still unable to catalyze the glucuronidation of bilirubin.
Crigler-Najjar syndrome, type II is associated with other mutation(s) that lead to a reduced activity of the
mutated UGT1A1 enzyme, which causes a hyperbilirubinemia with levels of total serum bilirubin from 6 to
20 mg/dL. In this case phenobarbital treatment helps to lower bilirubin lever by more than 30%.

Dr Anand Chandrasekaran Annan Dr Atul Thatai

MD (American Board of Pathology) PhD, Biotechnology
PhD (Molecular & Cellular Pathology) HOD Molecular Diagnostics
HOD - Oncopathology NRL - Dr Lal PathLabs Ltd

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PatientReportSCSuperPanel.FLOWCYTO_DYNAMIC_SC (Version: 6)

*153672449*
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.

LPL - LPL-ROHINI (NATIONAL REFERENCE LAB)

SECTOR - 18, BLOCK -E ROHINI DELHI 110085

Name DUMMY N189 Collected 29/7/2020 1:59:00PM

Received 29/7/2020 3:51:13PM

Lab No. 153672449 Age: 35 Years Gender: Male Reported 31/7/2020 2:54:42PM

A/c Status P Ref By: UNKNOWN Report Status Final

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customer care Tel No. +91-11-39885050 for all queries related to test results.
(#) Sample drawn from outside source.

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