Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations.
Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia. Intra-ethnic differences in the genetic variation and haplotypes of UGT1A1 gene have been analyzed in the present study. Relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were also evaluated. We genotyped five functional polymorphisms including -3279T>G and -3156G>A in the enhancer region, (TA)6>7 in the TATA box, and 211G>A (G71R), 686C>A (P229Q) in the exon1 region of UGT1A1 in three groups of healthy Chinese ethnic populations, consisting of 264 subjects of She origin, 539 of Han origin and 273 of Dong origin. The distribution of -3279T>G, (TA)6>7, 211G>A of UGT1A1 differed greatly as between the three ethnic groups. All of six haplotypes differed considerably between at least two of the three groups, which highlighted the need to analyze clinically irinotecan toxicity relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population. Total bilirubin concentration in homozygous carriers of the -3279G and (TA)7 allele were significantly higher than those in heterozygous carriers or homozygous carriers of wild-type alleles. Carriers of the variant haplotypes (-3279G; -3156A; (TA)7; 211G; 686C) had higher serum T-Bil concentrations compared with the other groups. Our results indicate that heterogeneity among different ethnic populations is possibly the result of microevolution and is relevant to studies into the effect of tailored drug treatment.
Zhang
A
A
Bio-X Center, Shanghai Jiao Tong University, Shanghai, China.
Xing
Q
Q
Qin
S
S
Du
J
J
Wang
L
L
Yu
L
L
Li
X
X
Xu
L
L
Xu
M
M
Feng
G
G
He
L
L
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000378:metabolism; D044466:Asian People / Q000235:genetics*; D001663:Bilirubin / Q000097:blood; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism; D002681:China; D005006:Ethnicity / Q000235:genetics*; D005091:Exons; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006932:Hyperbilirubinemia / Q000201:enzymology / Q000235:genetics; D000077146:Irinotecan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012016:Reference Values; D016385:TATA Box / Q000235:genetics; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D001663:Bilirubin; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme