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UGT1A1 (TA)n promoter genotype: Diagnostic and population pharmacogenetic marker in Serbia

M Vukovic
M Vukovic
, 
N Radlovic
N Radlovic
, 
Z Lekovic
Z Lekovic
, 
K Vucicevic
K Vucicevic
, 
N Maric
N Maric
, 
N Kotur
N Kotur
, 
V Gasic
V Gasic
, 
M Ugrin
M Ugrin
, 
M Stojiljkovic
M Stojiljkovic
, 
L Dokmanovic
L Dokmanovic
, 
B Zukic
B Zukic
 and 
S Pavlovic
S Pavlovic
   | Oct 29, 2018
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Article Category: Original Article
Published Online: Oct 29, 2018
Page range: 59 - 68
DOI: https://doi.org/10.2478/bjmg-2018-0012
Keywords
© 2018 Vukovic M, Radlovic N, Lekovic Z, Vucicevic K, Maric N, Kotur N, Gasic V, Ugrin M, Stojiljkovic M, Dokmanovic L, Zukic B, Pavlovic S, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

(a) UGT1A1 (TA)n promoter PCR products on 15.0% acrylamide gel electrophoresis stained with Ag-nitrate. Wells 1 and 4: 6/6 TA repeats (71 bp); well 2: 7/7 TA repeats (73 bp); well 5: 6/7 TA repeats (71 and 73 bp); well 3: 5 bp DNA ladder. (b) Electophoretograms obtained with fragment length analysis of UGT1A1 (TA)n promoter repeats. The upper peak is 7/7 TA repeats (102 bp); the lower peak is 6/6 TA repeats (100 bp). (c) Electophoretogram obtained with sequencing analysis of promoter of UGT1A1 gene with 6/6 TA repeats. (d) Electophoretogram obtained with sequencing analysis of promoter of UGT1A1 gene with 7/7 TA repeats.
(a) UGT1A1 (TA)n promoter PCR products on 15.0% acrylamide gel electrophoresis stained with Ag-nitrate. Wells 1 and 4: 6/6 TA repeats (71 bp); well 2: 7/7 TA repeats (73 bp); well 5: 6/7 TA repeats (71 and 73 bp); well 3: 5 bp DNA ladder. (b) Electophoretograms obtained with fragment length analysis of UGT1A1 (TA)n promoter repeats. The upper peak is 7/7 TA repeats (102 bp); the lower peak is 6/6 TA repeats (100 bp). (c) Electophoretogram obtained with sequencing analysis of promoter of UGT1A1 gene with 6/6 TA repeats. (d) Electophoretogram obtained with sequencing analysis of promoter of UGT1A1 gene with 7/7 TA repeats.

Figure 2

Median and interquartile range of ratios between levels of unconjugated bilirubin after phenobarbitone test comparing to levels of bilirubin before the test of unconjugated bilirubin according to GS risk groups (GS non-risk, GS risk) (Mann-Whitney test, p = 0.040).
Median and interquartile range of ratios between levels of unconjugated bilirubin after phenobarbitone test comparing to levels of bilirubin before the test of unconjugated bilirubin according to GS risk groups (GS non-risk, GS risk) (Mann-Whitney test, p = 0.040).

Levels of unconjugated bilirubin in pediatric Gilbert syndrome patients.

ParametersUnconjugated Bilirubin in GS Risk Group (μmol/L)

The results are presented as mean ± standard deviations.

Unconjugated Bilirubin in GS Non-Risk Group (μmol/L)

The results are presented as mean ± standard deviations.

p Values

The p values were assessed using the Mann-Whitney test.

At diagnosis27.51 ± 19.1616.92 ± 7.570.079
After hypocaloric test62.02 ± 43.8541.40 ± 14.670.240
After phenobarbitone test18.01 ± 14.5714.23 ± 6.710.626

List of primers used for sequencing of the UGT1A1 coding and nearby intronic regions.

PrimerSequences (5’>3’)Temperature Annealing (°C)
UGT1A1: ex1-1FGCT ACC TTT GTG GAC TGA CAG C60
UGT1A1: ex1-1RCCA TGA GCT CCT TGT TGT GCA G
UGT1A1: ex1-2FGCC ATT CCA AAG GGA GGA TG57
UGT1A1: ex1-2RGAT GAT GCC AAA GAC AGA CTC AAA C
UGT1A1: int1ex2FCTG TAA GCA GGA AAC CCT TCC TC58
UGT1A1: int1ex2RGGA TTA ATA GTT GGG AAG TGG CAG G
UGT1A1: ex3FAAG TTG CCA GTC CTC AGA AGC60
UGT1A1: ex3RTGT TAC TCA CAT GCC CTT GCA G
UGT1A1: ex4int4FTGC AAG GGC ATG TGA GTA ACA C58
UGT1A1:ex4int4RGCA CTC CAG CCT AGG TGA C
UGT1A1: ex5FCAG GTT TCC TTT CCC AAG TTT GG58
UGT1A1: ex5RCAC TCT GGG GCT GAT TAA TTT ATG C

The distribution of UGT1A1 (TA)n promoter repeats in Gilbert syndrome patients and control groups.

GS Patients (n = 51)Controls (n = 100)
Repeatsn%Repeatsn%
6/623.926/63737.0
6/7815.876/74747.0
7/73976.477/71616.0
7/823.927/800.0
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