Gilbert s syndrome

Increased Risk of Toxicity in Cancer Patients with Gilbert s Syndrome... 

Wasserman E, Myara A, Lokiec F et al. Severe CPT-11 toxicity in patients with Gilbert s syndrome two case report. Ann Oncol 1997 8 1049-1051. 

Bosma PJ, Chowdhury JR, Barker C et al. The genetic basis of the reduced expression of bilimbin UDP-glucuronosyl-transferase 1 in Gilbert s syndrome. 

Owens D, Evans L. Population studies on Gilbert s syndrome. J Med Genet 1975 12 152-156. 

Iolascon A, Faienza MF, Centra M et al. (TA)8 allele in the UGT1A1 gene promoter of a Caucasian with Gilbert s syndrome. Haematologica 1999 84 106-109. 

Sato H, Adachi Y, Koiwai O. The genetic basis of Gilbert s syndrome. Lancet 1996 347 557-558. 

Delayed uptake of bilirubin has been described in mutant Southdown sheep (CIO), suggesting a deficiency in cytoplasmic organic anion-binding protein. Measurements of the conjugating enzymes are desirable. Conceivably, a decreased conjugating capacity could influence the uptake, as is suggested from studies on patients with Gilbert s syndrome (B14, B15,B18). 

B15. Black, M., and Billing, B. H., Hepatic bilirubin UDP-gluouronyl-transferase activity in liver disease and Gilbert s syndrome. New Engl. J. Med. 280,1266-1271 (1969). 

B16. Black, M., and Sherlock, S., Treatment of Gilbert s syndrome with phenobarbi-tone. Lancet i, 1359-1362 (1970). 

The most extensively investigated polymorphism is a variation of the number of TA repeats (A(TA) TAA, n = 5-8) in the promoter region. The wild-type allele contains six [(TA)6] repeats that are located -53 to -A2 from the translational start codon. UGT1A1 28 [(TA)7], a common variation in Gilbert s syndrome (25,26), has an in vitro translational activity that is 63% of the wild-type allele (27). Minor TA variations include 36 n = 5) and 37 n= 8), which result in enhanced and reduced, respectively, transcriptional activity in vitro (Table 1). 

Aono S, Adachi Y, Uyama E et al. Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert s syndrome. Lancet 1995 345 958-959. 

Kohle C, Mohrle B, Munzel PA et al. Frequent co-occurrence of the TATA box mutation associated with Gilbert s syndrome (UGT1AD28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6 "2 and UGT1A7 "3) in Caucasians and Egyptians. A/oc/jera Pharmacol 2003 65 1521-1527. 

UDP-gluconosyltransferase Gene Promoter and Gilbert s Syndrome , Lancet, 347, 578-581 (1996). 

Human UGT1A genes contains multiple polymorphisms that alter enzyme structure (161) as well as a TATA-box promoter polymorphism, UGT1AT28, that leads to reduced constitutive expression in conditions such as Gilbert s syndrome (162,163) and to decreased conjugation of 2-hydroxyestradiol (164). However, there is no evidence that the variant UGT1AT28 allele affects induction of UGT1A1. 

Monaghan G, Ryan M, Seddon R, et al. Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert s syndrome [see comments]. Lancet 1996 347(9001) 578-581. 

Ferraris A, D Amato G, Nobili V, et al. Combined test for UGT1A1 -3279T->G and A(TA)nTAA polymorphisms best predicts Gilbert s syndrome in Italian pediatric patients. Genet Test 2006 10(2) 121-125. 

Ullrich D, Sieg A, Blume R, et al. Normal pathways for glucuronidation, sulphation and oxidation of paracetamol in Gilbert s syndrome. Eur J Clin Invest 1987 17(3) 237-240. 

Herman RJ, Chaudhary A, Szakacs CB. Disposition of lorazepam in Gilbert s syndrome effects of fasting, feeding, and enterohepatic circulation. J Clin Pharmacol 1994 34(10) 978-984. 

Posner J, Cohen AF, Land G, et al. The pharmacokinetics of lamotrigine (BW430C) in healthy subjects with unconjugated hyperbilirubinaemia (Gilbert s syndrome). Br J Clin Pharmacol 1989 28(1) 117-120. 

Finally, there are hereditary causes of non-conjugated, nonhemolytic hyperbilirubinemias. These are Crigler-Najjar types 1 and 2 and Gilbert s syndrome (discussed in the section on Genetic Diseases of Bilirubin Metabolism). 

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