ABCB4 gene mutation-associated cholelithiasis in adults.
OBJECTIVE
We recently put forward arguments in favor of ABCB4 gene (adenosine triphosphate-binding cassette, subfamily B, member 4) defects as a risk factor for symptomatic cholelithiasis in adults. In this study, we characterized ABCB4 gene mutations in a series of patients with symptomatic cholelithiasis to determine the genetic basis and the clinical phenotype of ABCB4 gene mutation-associated cholelithiasis.


METHODS
We analyzed the entire ABCB4 gene coding sequences in a first group of 32 patients who had a clinical history compatible with the syndrome previously described, in a second group of 28 patients who presented with a classic gallstone disease that justified a cholecystectomy, and in a third group of 33 patients without a history of cholelithiasis.


RESULTS
We identified both heterozygous and homozygous ABCB4 gene point mutations in 18 of 32 (56%) patients who presented with clinical criteria of the syndrome, whereas no mutation was detected in the 2 other groups of patients (P < 0.001). Three independent clinical features were strongly associated with point mutations: recurrence of symptoms after cholecystectomy (odds ratio, 8.5); intrahepatic hyperechoic foci, intrahepatic sludge, or microlithiasis (odds ratio, 6.1); and age <40 years at the onset of symptoms (odds ratio, 3.0). ABCB4 gene point mutations were detected exclusively in the patients who showed 2 or 3 of these clinical features.


CONCLUSIONS
Our results show that ABCB4 gene mutations represent a major genetic risk factor in a symptomatic and recurring form of cholelithiasis in young adults.
Rosmorduc
Olivier
O
Service d'Hépatologie, Paris, France.
Hermelin
Brigitte
B
Boelle
Pierre-Yves
PY
Parc
Rolland
R
Taboury
Jacques
J
Poupon
Raoul
R
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D002769:Cholelithiasis / Q000209:etiology / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D010743:Phospholipids; D002784:Cholesterol; C095122:multidrug resistance protein 3