Received for publication January 4, 2007.
Revised March 22, 2007.
Accepted for publication April 30, 2007.

UDP-Glucuronosyltransferase 1A1 Gene Polymorphisms and Total Bilirubin Levels in an Ethnically Diverse Cohort of Women

Abstract

Objectives: To investigate variations in UGT1A1 polymorphisms and haplotypes among African American and Caucasian women and to assess whether variants other than UGT1A1*28 are associated with total serum bilirubin levels. Methods: The (TA)n repeats and 14 single nucleotide polymorphisms (SNPs) in the UGT1A1 gene were genotyped in 335 African Americans and 181 Caucasians. Total serum bilirubin levels were available in a subset of 125 women. Results: Allele frequencies of all SNPs and (TA)n repeats were significantly different between African Americans and Caucasians. In Caucasians, three common haplotypes accounted for 71.8% of chromosomes while five common haplotypes accounted for only 46.6% of chromosomes in African Americans. Mean total serum bilirubin levels were significantly lower (p=0.005) in African Americans (0.36 mg/dl) than in Caucasians (0.44 mg/dl). The (TA)n repeats explained a significant amount of variation in total bilirubin levels (R²=0.27, p<0.0001) while other SNPs were less correlative. Conclusions: Significant variations in UGT1A1 haplotype structure exist between African Americans and Caucasians in this relatively large cohort of women. UGT1A1's correlation with total bilirubin levels was mainly due to (TA)n repeats in Caucasians but a clear correlation was not observed in African Americans due to the high diversity of haplotypes and a small sample size. These data have implications in design of epidemiologic studies of cancer susceptibility and pharmacogenetic studies for adverse drug reactions in populations of African ancestry.

Key words: antioxidants, ethnic differences, genetic polymorphism, genotype, human genetics, UDP glucuronyltransferases