title: Genetic variability, haplotypes, and htSNPs for exons 1 at the human UGT1A locus.
abstract: UDP-Glucuronosyltransferases (UGTs) are a superfamily of enzymes responsible for glucuronidation of xenobiotics and endobiotics. Genetic polymorphisms have been identified in the promoter and exonic regions of several UGT genes. The UGT1As on chromosome 2q37 have unique exons 1 but share the remainder of their coding sequence. We screened exon 1 of each of the nine functional UGT1As in Asians (n=46) and Caucasians (n=92) with the aim of determining linkage disequilibrium (LD) and haplotypes across the entire locus in both populations. For polymorphisms in UGT 1A3, 1A4, 1A5, 1A7, and 1A8, we observed significant differences in the allele frequency between the two populations. The haplotype block structure across the UGT1A locus was constructed using all 83 polymorphisms and showed four and five haplotype blocks in Caucasians and Asians, respectively. There was long-distance LD between UGT pairs: 1A8 and 1A10; 1A1 and 1A3; 1A1 and 1A6; 1A6 and 1A7; and 1A7 and 1A9. Whereas both ethnic groups shared some haplotype-tagging SNPs (htSNPs), Caucasians and Asians also had unique htSNPs. This was partly due to the fact that rare variants (<5% allele frequency) were included in our analyses. Haplotypes with frequencies >5% represented only 60% of Caucasian and 65% of Asian UGT1A haplotypes. Differences in haplotype distribution patterns suggest individual and ethnic differences in glucuronidation capacity.
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
authors.forename: Sushma S
authors.initials: SS
authors.lastname: Thomas
authors.forename: Shuying S
authors.initials: SS
authors.lastname: Li
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Jeannette
authors.initials: J
authors.lastname: Bigler
mesh_terms: D044466:Asian People / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005787:Gene Frequency; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044465:White People / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme