ATP-binding cassette transporter ABCG2 (BCRP) and ABCB1 (MDR1) variants are not associated with disease susceptibility, disease phenotype response to medical therapy or need for surgeryin Hungarian patients with inflammatory bowel diseases.
OBJECTIVE
MDR1 (ABCB1), a member of the ATP-binding cassette (ABC) transporters, is an attractive candidate gene for the pathogenesis of inflammatory bowel diseases (IBD) and perhaps for response to therapy. Since limited data are available on MDR1 and ABCG2 polymorphisms in East European IBD patients, the aim of this study was to investigate ABCG2 and MDR1 variants and responses to medical therapy and/or disease phenotype in Hungarian patients.


METHODS
A total of 414 unrelated IBD patients (Crohn's disease (CD): 265, age: 35.2+/-12.1 years, duration: 8.7+/-7.6 years and ulcerative colitis (UC): 149, age: 44.4+/-15.4 years, duration: 10.7+/-8.9 years) and 149 healthy subjects were investigated. ABCG2 G34A, C421A and MDR1 C3435T, G2677T/A single nucleotide polymorphisms (SNPs) were detected using real-time polymerase chain reaction (PCR). Detailed clinical phenotypes were determined by reviewing the medical charts.


RESULTS
The frequency of the ABCG2 and MDR1 SNPs was not significantly different among IBD, CD, UC patients and controls. There was no difference in risk for steroid resistance in CD patients carrying variant ABCG2 (19.6% versus non-carriers 18.4%, p=NS) or MDR1 3435T (CC: 22.2% versus CT/TT: 17.6%) alleles. In addition, carriage of the variant allele was not associated with disease phenotype, presence of extra-intestinal manifestations, smoking, response to infliximab therapy or the need for surgery. In UC, the carriage of variant ABCG2 alleles seemed to be preventive for arthritis (15.5% versus 31.7%, OR: 0.39, 95% CI: 0.16-0.98).


CONCLUSIONS
MDR1 and ABCG2 SNPs were not associated with disease susceptibility or disease phenotype in Hungarian patients, and variant alleles did not predict the response to medical therapy or the need for surgery. Further studies are needed to clarify the association between the presence of ABCG2 variants and arthritis in UC.
Fischer
Simon
S
1st Department of Medicine, Semmelweis University, Budapest, Hungary.
Lakatos
Peter Laszlo
PL
Lakatos
Laszlo
L
Kovacs
Agota
A
Molnar
Tamas
T
Altorjay
Istvan
I
Papp
Maria
M
Szilvasi
Aniko
A
Tulassay
Zsolt
Z
Osztovits
Janos
J
Papp
Janos
J
Demeter
Pal
P
Schwab
Richard
R
Tordai
Attila
A
Andrikovics
Hajnalka
H
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000328:Adult; D013505:Digestive System Surgical Procedures / Q000706:statistics & numerical data*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006814:Hungary; D015212:Inflammatory Bowel Diseases / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D027361:Organic Anion Transporters / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters