NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients.
OBJECTIVE
To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).


METHODS
We analyzed 1707 Hungarian and Czech subjects with Crohn's disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCycler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts.


RESULTS
NKX2-3 rs10883365 variant allele was associated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associated with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathioprine, efficacy of infliximab, or need for surgery.


CONCLUSIONS
NKX2-3 and IRGM are susceptibility loci for IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.
Department of Molecular Diagnostics, Hungarian National Blood Transfusion Service, H-1113 Budapest, Hungary.
Nora
N
Meggyesi
Lajos S
LS
Kiss
Magdalena
M
Koszarska
Martin
M
Bortlik
Dana
D
Duricova
Laszlo
L
Lakatos
Tamas
T
Molnar
Martin
M
Leniček
Libor
L
Vítek
Istvan
I
Altorjay
Maria
M
Papp
Zsolt
Z
Tulassay
Pal
P
Miheller
Janos
J
Papp
Attila
A
Tordai
Hajnalka
H
Andrikovics
Milan
M
Lukas
Peter Laszlo
PL
Lakatos
D000328:Adult; D003604:Czechoslovakia; D005006:Ethnicity / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006814:Hungary; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D014157:Transcription Factors / Q000235:genetics*
C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; C534957:NKX2-3 protein, human; D014157:Transcription Factors; D019204:GTP-Binding Proteins; C513539:IRGM protein, human