Microarray with LNA-probes for genotyping of polymorphic variants of Gilbert’s syndrome gene UGT1A1(TA)n

AbstractGilbert’s syndrome is a common metabolic dysfunction characterized by elevated levels of unconjugated bilirubin in the bloodstream. This condition is usually caused by additional (TA) insertions in a promoter region of the uridine diphosphate glucuronosyltransferase 1A1 (The technique is based on hybridization analysis of a pre-amplified segment of theA microarray has been developed to identify both common and rare variants ofThe developed microarray-based approach for identification of polymorphic variants of the

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Genetic polymorphisms of bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects

Journal of Gastroenterology and Hepatology ◽

10.1111/j.1440-1746.2004.03370.x ◽

2004 ◽

Vol 19 (9) ◽

pp. 1023-1028 ◽

Cited By ~ 68

Author(s):

KEISUKE TAKEUCHI ◽

YOSHINAO KOBAYASHI ◽

SHIGENORI TAMAKI ◽

TOMOAKI ISHIHARA ◽

YOSHIHIRO MARUO ◽

...

Keyword(s):

Genetic Polymorphisms ◽

Japanese Patients ◽

Uridine Diphosphate ◽

Gilbert’S Syndrome ◽

Uridine Diphosphate Glucuronosyltransferase ◽

Gilbert's Syndrome ◽

Japanese Subjects

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How dangerous Gilbert's syndrome is

Spravočnik vrača obŝej praktiki (Journal of Family Medicine) ◽

10.33920/med-10-2110-01 ◽

2021 ◽

pp. 8-12

Author(s):

Roman Petrovich Stepchenkov

Keyword(s):

Pathological Condition ◽

Inhibitory Effect ◽

Unconjugated Bilirubin ◽

Breakdown Product ◽

Gilbert’S Syndrome ◽

Gilbert's Syndrome ◽

Bilirubin Metabolism ◽

Gallbladder Dyskinesia ◽

Conjugation Process ◽

Loss Of Appetite

Gilbert's syndrome is a benign (functional) hyperbilirubinemia, which is based on a hereditary disorder of bilirubin metabolism, as a result of which the concentration of unbound bilirubin can increase several times. Bilirubin, being a breakdown product of hemoglobin, circulates through the bloodstream, combining with albumin molecules. Such bilirubin is called indirect. In the endoplasmic reticulum, it is conjugated; the enzyme glucuronyltransferase is responsible for this process. In Gilbert's syndrome, as a result of insufficient production of this enzyme, the conjugation process is disrupted, and, as a result, the concentration of unconjugated bilirubin increases. According to statistics, this pathological condition is observed in about 5 % of Russians. This syndrome was first described in 1901 by the French physician Augustin Nicolas Gilbert, and was subsequently named after him. The literature also contains references to this syndrome, described as «constitutional hepatic dysfunction», «familial non-hemolytic hyperbilirubinemia», «idiopathic non-conjugated hyperbilirubinemia». Gilbert's syndrome is inherited in an autosomal recessive manner; men get ill 3–4 times more often than women. A number of scientists associate this with a possible inhibitory effect of testosterone on the enzyme UDP-GT1, which breaks down bilirubin. Clinically, Gilbert's syndrome is manifested by episodes of jaundice caused by an increase in the level of unconjugated bilirubin in the blood serum. Against the background of icterus of the sclera and skin, there is increased fatigue, the appearance of a feeling of bitterness in the mouth, loss of appetite, nausea, and sometimes vomiting. The association of Gilbert's syndrome with functional disorders of the biliary tract, in particular, with gallbladder dyskinesia, is often noted.

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Phenobarbital for Long-Term Management of Marked Hyperbilirubinemia.

Blood ◽

10.1182/blood.v114.22.5089.5089 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5089-5089

Author(s):

A. Majid Shojania

Keyword(s):

Hemolytic Anemia ◽

Skin Color ◽

Conflicts Of Interest ◽

Hereditary Hemochromatosis ◽

High Serum ◽

Hfe Gene ◽

Therapeutic Trial ◽

Uridine Diphosphate ◽

Gilbert’S Syndrome ◽

Gilbert's Syndrome

Abstract 5089 Gilbert's syndrome (GS) is associated with a mild chronic unconjugated hyperbilirubinemia, due to partial deficiency of bilirubin uridine diphosphate glucuronyl transferase (UDPGT). Phenobarbital is a known inducer of hepatic UDPGT and has been used in hyperbilirubinemia of newborns. It has also been used as a test for support of the diagnosis of GS. However, because hyperbilirubinemia of GS is mild and harmless, phenobarbital is not used for treatment of hyperbilirubinemia in adults. I report a case of a 46-year-old woman who, because of having chronic hereditary hemolytic anemia and GS, had marked hyperbilirubinemia with psychosocial problems, as the result of her hyperbilirubinemia and her skin color, which responded well to chronic phenobarbital treatment. Case report- CH was diagnosed to have hereditary high phosphatidylcholine hemolytic anemia (HHPCHA) at the age of 23. She was seen again at the age of 30 because of very high serum ferritin and iron saturation which seemed disproportionally high for the degree of her mild hemolytic anemia (51Cr RBC survival T½ of 16.5 days). Further investigation revealed that she had hereditary hemochromatosis due to homozygosity for H63D HFE gene. She was started on phlebotomies initially weekly and later on every 2-3 months to control her iron overload. During the follow-up it was noted that her serum unconjugated bilirubin (SUB) was persistently much higher than is expected from her mild hemolytic anemia (up to 288 μmol/L). Since she had no abnormality of liver function tests, I suspected that she also has Gilbert's syndrome. In September 2008 her blood was sent for genetic testing which showed that she has an additional TA repeat [(TA)7/(TA)7], confirming the diagnosis of GS. On January 21, 2009 when her SUB was 149 μmol/L, she expressed concern that her friends and coworkers keep making fun of her, because of the orange color of her face and sclera. She was started on phenobarbital 30 mg daily for a month and then 60 mg daily. This therapy rapidly brought her bilirubin down and changed the color of her face to normal, making her very happy. Her SUB on February 20, March 20 and June 30, 2009 were 103, 63 and 37 μmol/L, respectively. Conclusion Gilbert's syndrome is a common hereditary disorder that can aggravate hyperbilirubinemia of chronic hemolytic anemia. However, this association is often unrecognized, because many physicians attribute the hyperbilirubinemia to hemolysis and do not look for associated GS. In chronic hemolytic anemias, if hyperbilirubinemia is more than expected, the possibility of an associated GS should be considered. If such association exists, small daily doses of phenobarbital can markedly reduce this hyperbilirubinemia and improve the psychosocial effects of hyperbilirubinemia. Furthermore, marked reduction of bilirubin, following the therapeutic trial of Phenobarbital, will confirm the association of GS with hemolytic anemia. Disclosures No relevant conflicts of interest to declare.

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Unconjugated Bilirubin and an Increased Proportion of Bilirubin Monoconjugates in the Bile of Patients with Gilbert's Syndrome and Crigler-Najjar Disease

Journal of Clinical Investigation ◽

10.1172/jci108877 ◽

1977 ◽

Vol 60 (5) ◽

pp. 970-979 ◽

Cited By ~ 92

Author(s):

Johan Fevery ◽

Norbert Blanckaert ◽

Karel P. M. Heirwegh ◽

Anne-Marie Préaux ◽

Pierre Berthelot

Keyword(s):

Unconjugated Bilirubin ◽

Gilbert’S Syndrome ◽

Gilbert's Syndrome

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Statin Intolerance in a Patient with Gilberts Syndrome and Hypercholesterolemia

Experimental and Clinical Endocrinology & Diabetes Reports ◽

10.1055/s-0042-113873 ◽

2016 ◽

Vol 3 (01) ◽

pp. e8-e10 ◽

Cited By ~ 1

Author(s):

I. Jialal ◽

D. Siegel

Keyword(s):

Ldl Cholesterol ◽

Unconjugated Bilirubin ◽

Familial Combined Hyperlipidemia ◽

Statin Intolerance ◽

Gilbert’S Syndrome ◽

Cholesterol Levels ◽

Gilbert's Syndrome ◽

Cytochrome 450 ◽

Statin Drugs

Abstract Background: Statin intolerance especially myalgias can be a serious problem. Whilst it is well know that drugs that compete for Cytochrome 450 system can result in myalgias there is sparse data on the role of glucuronidation of statins contributing to statin intolerance We report on a 60 year old male with Hypercholesterolemia (HC) who was referred for management of his HC since he had statin intolerance manifesting as myalgias and was shown to have Gilbert’s Syndrome. Case Report: Investigation of this patient revealed he had Familial Combined Hyperlipidemia with a LDL-cholesterol of 189 mg/dl. He was also diagnosed with Gilbert’s Syndrome since he had elevated unconjugated bilirubin with no evidence of liver disease or hemolysis. The combination of Niacin, Cholestyramine and ezetimibe resulted in a successful decrease in his LDL-cholesterol to 114 mg/dl. Discussion: We believe that his Gilberts Syndrome resulted in an impairment in glucuronidation of statin drugs resulting in an increase in free drug levels and myalgias. We caution that clinicians should consider this possibility when confronted with a patient with both isolated elevations of unconjugated bilirubin and increase LDL-cholesterol levels before commencing statin therapy.

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Bone Mineral Densities in Individuals with Gilbert’s Syndrome: A Cross-Sectional, Case-Control Pilot Study

Canadian Journal of Gastroenterology ◽

10.1155/2009/635126 ◽

2009 ◽

Vol 23 (6) ◽

pp. 431-436 ◽

Cited By ~ 2

Author(s):

GY Minuk ◽

R Greenberg ◽

J Uhanova ◽

K Hawkins ◽

WD Leslie

Keyword(s):

Pilot Study ◽

Bone Mineral ◽

Case Control ◽

Unconjugated Bilirubin ◽

Cross Sectional ◽

Gilbert’S Syndrome ◽

Control Subjects ◽

Gilbert's Syndrome ◽

Z Scores ◽

Total Body

BACKGROUND: Unconjugated bilirubin inhibits osteoblastic proliferative activity in vitro, raising the possibility that Gilbert’s syndrome (GS) patients are at increased risk of osteoporosis.OBJECTIVES: To compare bone mineral density (BMD), serum parathyroid hormone (PTH), C-telopeptide (CTX) and osteocalcin levels in GS subjects versus matched controls in a cross-sectional, case-control study.METHODS: BMD determinations were obtained with central dual-energy x-ray absorptiometry. Serum PTH, CTX and osteocalcin levels were measured by enzyme immunoassay.RESULTS: A total of 17 GS and 30 control subjects were studied. Overall, there were no significant differences in BMD, PTH, CTX or osteocalcin levels between the two groups. However, when older (older than 40 years of age) and younger (40 years of age and younger) cohorts were considered separately, the older GS cohort had significantly decreased total hip BMD, T scores and Z scores, and femoral neck BMD, T scores and Z scores (P<0.005 for each parameter, respectively) compared with older control subjects. Serum osteocalcin levels were lower in the older versus younger GS cohort (P=0.006). An inverse correlation existed between all subjects’ serum unconjugated bilirubin levels and total body BMD determinations (r=−0.42; P=0.04). On univariate analysis, the association between serum unconjugated bilirubin and total body BMD was not significant (P=0.066), nor was serum unconjugated bilirubin identified as a risk factor for low BMD when entered into multivariate analyses.CONCLUSIONS: The results of the present pilot study warrant further research involving larger numbers of subjects and longitudinal measurements to determine whether GS is associated with decreased BMD, particularly in older GS subjects.

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