title: Combined UGT1A1 and UGT1A7 variant alleles are associated with increased risk of Gilbert's syndrome in Taiwanese adults.
abstract: 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 -57UGT1A7 and 622UGT1A7 loci (D' = 1.00 and r(2) = 1.00), -57UGT1A7 and 211UGT1A1 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 -57UGT1A7 (T>G) is highly associated with UGT1A7*3 and moderately associated with 211UGT1A1 (G>A). Certain UGT1A1/UGT1A7 combined genotypes are risk factors of GS.
authors.affiliation: College of Medicine and Health, Fooyin University, 151 Chin-Hsueh Road, La-Tiao Hsiang, Kaohsiung Hsien 831, Taiwan. sjteng@mail.fy.edu.tw
authors.forename: H-C
authors.initials: HC
authors.lastname: Teng
authors.forename: M-J
authors.initials: MJ
authors.lastname: Huang
authors.forename: K-S
authors.initials: KS
authors.lastname: Tang
authors.forename: S-S
authors.initials: SS
authors.lastname: Yang
authors.forename: C-S
authors.initials: CS
authors.lastname: Tseng
authors.forename: C-S
authors.initials: CS
authors.lastname: Huang
mesh_terms: D000483:Alleles; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005878:Gilbert Disease / Q000208:ethnology / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D012306:Risk; D012307:Risk Factors; D013624:Taiwan; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C107611:UDP-glucuronosyltransferase, UGT1A7