Analysis of inherited genetic variations at the UGT1 locus in the French‐Canadian population

@article{Mnard2009AnalysisOI,
  title={Analysis of inherited genetic variations at the UGT1 locus in the French‐Canadian population},
  author={Vincent M{\'e}nard and Hugo Girard and Mario Harvey and Louis P{\'e}russe and Chantal Guillemette},
  journal={Human Mutation},
  year={2009},
  volume={30}
}
The UDP‐glucuronosyltransferase UGT1 locus is composed of nine exon 1s, each flanked by a unique promoter region, and common exons (2, 3, 4, and the alternatively spliced exons 5a and 5b). Here, we characterized the genetic architecture of the UGT1 gene in a Caucasian sample. Overall, 98 variations in regulatory domains, exons and exon–intron boundaries were genotyped in 254 unrelated subjects, including 12 unreported UGT1 polymorphisms. We determined allele frequencies, computed pairwise… 
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References

SHOWING 1-10 OF 68 REFERENCES
Genetic variability, haplotypes, and htSNPs for exons 1 at the human UGT1A locus
TLDR
Differences in haplotype distribution patterns suggest individual and ethnic differences in glucuronidation capacity in UDP‐Glucuronosyltransferases.
Haplotype structures of the UGT1A gene complex in a Japanese population
TLDR
Important haplotypes and their linkages were identified among the UGT1A gene blocks (and segments), which should be considered in pharmacogenetic studies.
Genetic Variations and Haplotypes of UDP-glucuronosyltransferase 1A Locus in a Korean Population
TLDR
The results suggest that genetic polymorphisms of the UGT1A locus differ between Koreans and other ethnic populations, and should be considered in pharmacogenetic studies.
Comparative genomics analysis of human sequence variation in the UGT1A gene cluster
TLDR
The results suggest that rare functional gene variants and inter-population variability must be considered in the interpretation of association studies between UGT1A and drug metabolism/toxicity phenotypes.
A novel polymorphism in the promoter region of human UGT1A9 gene (UGT1A9*22) and its effects on the transcriptional activity.
TLDR
The mutant allele with one base insertion in the promoter region of the UGT1A9 gene would alter the level of enzyme expression and the metabolism of those drugs that are substrates of UGT 1A9.
Identification of common polymorphisms in the promoter of the UGT1A9 gene: evidence that UGT1A9 protein and activity levels are strongly genetically controlled in the liver.
TLDR
This is the first study to demonstrate that naturally occurring sequence variations in the UGT1A9 promoter are informative in predicting the levels of protein and glucuronidating activity, providing a potential mechanism for interindividual variation in UGT 1A9-mediated metabolism.
Variation of hepatic glucuronidation: Novel functional polymorphisms of the UDP‐glucuronosyltransferase UGT1A4
TLDR
Two polymorphisms of the hepatic UGT1A4 protein show a differential metabolic activity toward mutagenic amines and endogenous steroids, altering hepatic metabolism and detoxification.
Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells.
TLDR
It is suggested that common genetic variation in human UGT1A6 confers functionally significant differences in biochemical phenotype as assessed in human tissue and cultured cells expressing recombinant allozymes.
Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 gene.
TLDR
The expression pattern of UGT1A7 studied herein and its catalytic activity profile suggest a possible role in the detoxification and elimination of carcinogenic products in lung, and it is suggested that further studies are needed to investigate the impact of the low UGT2A7 conjugator genotype on individual susceptibility to chemical-induced diseases and responses to therapeutic drugs.
Polymorphisms of the human UDP-glucuronosyltransferase (UGT) 1A7 gene in colorectal cancer
TLDR
A potential novel risk factor in sporadic colorectal cancer which may contribute to the identification of risk groups and to the elucidation of factors involved in colon carcinogenesis is identified.
...
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