Haplotypes of UGT1A1 and Total Bilirubin Concentration

J Health Info Stat > Volume 37(2); 2012 > Article

J Health Info Stat 2012;37(2):46-57.

Jung Ran Choi , Jeong Oh Kim , Dae Ryong Kang , In Kyung Kim , Hyun Suk Chae , Jin Hyoung Kang

ABSTRACT

Objectives:
UDP-glucuronosyltransferases (UGTs) are a superfamily of enzymes that catalyse the glucuronidation of xenobiotics and endobiotics. Genetic variations of UDP-glucuronyltransferase 1A1 (UGT1A1) influence the concentration of serum bilirubin. Design and
Methods:
We investigated the association of common polymorphisms and haplotypes of the UGT1A gene with bilirubin levels in 149 lung cancer patients. We genotyped UGT1A1 (-3279T>G, -3156G>A, -53(TA)6>7, 211G>A and 686C>A), UGT1A7 (UGT1A7*1, UGT1A7*2, and UGT1A7*4), and UGT1A9 (-118T9>10) variants by direct sequencing.
Results:
The three promoter polymorphisms are in close linkage disequilibrium. In 149 lung cancer patients, common haplotypes of UGT1A1 were: -3279T/211G/-53(TA)6 (frequency 0.56), -3279G/211G/-53(TA)6 (frequency 0.18), and -3279T/211A/-53(TA)6 (frequency 0.14). UGT1A1 -3279T>G, 211G>A, -53(TA)6/7, and UGT1A9 -118(T)9/10 variant were significantly associated with higher bilirubin concentrations.
Conclusions:
Three UGT1A1 promoter polymorphisms and haplotypes of the UGT1A1 gene are associated with total bilirubin concentrations in Korean lung cancer patients.

Key words: Bilirubin, haplotype, Lung cancer, UDP-glucuronosyltransferase