Absence of association between the multidrug resistance (MDR1) gene and inflammatory bowel disease.
OBJECTIVE
The multidrug resistance (MDR1) gene encodes for P-glycoprotein, a drug efflux pump. Mice deficient for the MDR1a gene spontaneously develop colitis. In humans, a polymorphism in exon 26 (C3435T) is associated with reduced expression levels and function of MDR1. Currently there are controversial data on the association between MDR1 and inflammatory bowel disease (IBD). The purpose of this study was to examine the involvement of this gene in IBD in a large population of Dutch patients with IBD and family-based controls.


METHODS
A total of 781 IBD cases and 315 controls were investigated. CD phenotypes were determined according to the Vienna Classification. Individuals were genotyped for six single nucleotide polymorphisms (SNPs) close to and in the MDR1 locus. This included the C3435T variant and six microsatellite markers close to and in the MDR1 locus. Single locus association analysis, haplotype association analysis and haplotype sharing statistic (HSS) were used to search for differences between patients and controls.


RESULTS
No association was observed for any of the SNPs with IBD as a group, or for ulcerative colitis, Crohn's disease and Crohn's disease phenotypes, either by single locus or haplotype association analysis or by HSS.


CONCLUSIONS
No association was observed between the MDR1 gene and IBD. This suggests that it is unlikely that MDR1 plays a role in IBD susceptibility.
Oostenbrug
Liekele E
LE
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands. l.e.oostenbrug@inter.nl.net
Dijkstra
Gerard
G
Nolte
Ilja M
IM
van Dullemen
Hendrik M
HM
Oosterom
Elvira
E
Faber
Klaas N
KN
de Jong
Dirk J
DJ
van der Linde
Klaas
K
te Meerman
Gerard J
GJ
van der Steege
Gerrit
G
Kleibeuker
Jan H
JH
Jansen
Peter L M
PL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1