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Combined UGT1A1 and UGT1A7 variant alleles are associated with increased risk of Gilbert’s syndrome in Taiwanese adults
Author(s) -
Teng HC,
Huang MJ,
Tang KS,
Yang SS,
Tseng CS,
Huang CS
Publication year - 2007
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2007.00873.x
Subject(s) - genotype , allele , biology , genetics , linkage disequilibrium , odds ratio , gene , haplotype , microbiology and biotechnology , medicine
Gilbert’s syndrome (GS) is caused by a reduction in the activity of hepatic bilirubin UDP‐glucuronosyltransferase (UGT). This reduction is associated with UGT1A1*28 and UGT1A1*6 polymorphisms. Recent research also showed that carriage of UGT1A1*6 allele were significantly related with UGT1A7*3 . Polymerase chain reaction–restriction fragment length polymorphism were utilized to determine UGT1A7 and UGT1A1 genes for 207 patients with GS and 207 gender/age‐matched healthy controls. For the 207 healthy controls, linkage disequilibrium was observed between −57 UGT1A7 and 622 UGT1A7 loci (D′ = 1.00 and r 2 = 1.00), −57 UGT1A7 and 211 UGT1A1 loci (D′ = 0.72 and r 2 = 0.36), respectively. A dose–response effect for number of at‐risk allele of UGT1A1 and risk for GS was noted (odds ratio (OR) = 8.19 for heterozygous UGT1A1*28 genotype; OR = 124.96 for homozygous UGT1A1*28 genotype; and p for trend <0.05). Patients with combined genotypes carrying UGT1A7 variant alleles and UGT1A1 variant alleles (including UGT1A1*28 and UGT1A1*6 ) are associated with increased risk of GS (OR = 13.96 for patients with combined genotype carrying at least one variant allele of UGT1A1 and UGT1A7 ). In conclusion, the −57 UGT1A7 (T>G) is highly associated with UGT1A7*3 and moderately associated with 211 UGT1A1 (G>A). Certain UGT1A1 / UGT1A7 combined genotypes are risk factors of GS.