PMID- 10579978
OWN - NLM
STAT- MEDLINE
DCOM- 19991222
LR  - 20220409
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 117
IP  - 6
DP  - 1999 Dec
TI  - Hepatocanalicular bile salt export pump deficiency in patients with progressive
      familial intrahepatic cholestasis.
PG  - 1370-9
AB  - BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis (PFIC), an
      inherited liver disease of childhood, is characterized by cholestasis and either 
      normal or increased serum gamma-glutamyltransferase activity. Patients with
      normal gamma-glutamyltransferase activity have mutations of the FIC1 locus on
      chromosome 18q21 or mutations of the BSEP gene on chromosome 2q24. Also, patients
      with bile acid synthesis defects have low gamma-glutamyltransferase activity. We 
      investigated expression of the bile salt export pump (BSEP) in liver samples from
      patients with a PFIC phenotype and correlated this with BSEP gene mutations.
      METHODS: BSEP and multidrug resistance protein 2 (MRP2) expressions were studied 
      by immunohistochemistry in liver specimens of 28 patients and BSEP gene mutation 
      analysis in 19 patients. Bile salt kinetics were studied in 1 patient. RESULTS:
      Sixteen of 28 liver samples showed no canalicular BSEP staining. Staining for
      MRP2 showed a normal canalicular pattern in all but 1 of these samples. Ten of 19
      patients showed BSEP gene mutations; BSEP protein expression was lacking in all
      10 patients. No mutations were found in 9 of 19 patients, and in all except 1,
      BSEP protein expression was normal. Bile salt concentration in bile of
      BSEP-negative/MRP2-positive PFIC patients was 0.2 +/- 0.2 mmol/L (n = 9; <1% of
      normal) and in BSEP-positive PFIC patients 18.1 +/- 9.9 mmol/L (n = 3; 40% of
      normal). The kinetic study confirmed the dramatic decrease of bile salt secretion
      in BSEP-negative patients. CONCLUSIONS: The findings show a close correlation
      between BSEP gene mutations and canalicular BSEP expression. Biliary secretion of
      bile salts is greatly reduced in BSEP-negative patients.
FAU - Jansen, P L
AU  - Jansen PL
AD  - Department of Gastroenterology, University Hospital Groningen, Groningen, The
      Netherlands. P.L.M.Jansen@int.azg.nl
FAU - Strautnieks, S S
AU  - Strautnieks SS
FAU - Jacquemin, E
AU  - Jacquemin E
FAU - Hadchouel, M
AU  - Hadchouel M
FAU - Sokal, E M
AU  - Sokal EM
FAU - Hooiveld, G J
AU  - Hooiveld GJ
FAU - Koning, J H
AU  - Koning JH
FAU - De Jager-Krikken, A
AU  - De Jager-Krikken A
FAU - Kuipers, F
AU  - Kuipers F
FAU - Stellaard, F
AU  - Stellaard F
FAU - Bijleveld, C M
AU  - Bijleveld CM
FAU - Gouw, A
AU  - Gouw A
FAU - Van Goor, H
AU  - Van Goor H
FAU - Thompson, R J
AU  - Thompson RJ
FAU - Muller, M
AU  - Muller M
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (ABCB11 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 11)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (DNA, Complementary)
RN  - 0 (Ion Pumps)
RN  - 9EI49ZU76O (multidrug resistance protein 3)
RN  - EC 2.3.2.2 (gamma-Glutamyltransferase)
SB  - IM
CIN - Gastroenterology. 1999 Dec;117(6):1496-8. PMID: 10579993
MH  - ATP Binding Cassette Transporter, Subfamily B/genetics/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 11
MH  - ATP-Binding Cassette Transporters/*biosynthesis/genetics/metabolism
MH  - Bile Acids and Salts/*metabolism
MH  - Cholestasis, Intrahepatic/enzymology/genetics/*metabolism
MH  - Chromosomes, Human, Pair 18
MH  - DNA, Complementary/analysis
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Immunohistochemistry
MH  - Ion Pumps/biosynthesis/immunology
MH  - Kinetics
MH  - Male
MH  - Mutation
MH  - Phenotype
MH  - Polymerase Chain Reaction
MH  - gamma-Glutamyltransferase/metabolism
EDAT- 1999/12/02 00:00
MHDA- 1999/12/02 00:01
CRDT- 1999/12/02 00:00
PHST- 1999/12/02 00:00 [pubmed]
PHST- 1999/12/02 00:01 [medline]
PHST- 1999/12/02 00:00 [entrez]
AID - S0016508599005545 [pii]
AID - 10.1016/s0016-5085(99)70287-8 [doi]
PST - ppublish
SO  - Gastroenterology. 1999 Dec;117(6):1370-9. doi: 10.1016/s0016-5085(99)70287-8.