NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients

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). We analyzed 1707 Hungarian and Czech subjects with Crohn's disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7...

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Veröffentlicht in:World journal of gastroenterology : WJG 2010-11, Vol.16 (41), p.5233-5240
Hauptverfasser: Meggyesi, Nora, Kiss, Lajos S, Koszarska, Magdalena, Bortlik, Martin, Duricova, Dana, Lakatos, Laszlo, Molnar, Tamas, Leniček, Martin, Vítek, Libor, Altorjay, Istvan, Papp, Maria, Tulassay, Zsolt, Miheller, Pal, Papp, Janos, Tordai, Attila, Andrikovics, Hajnalka, Lukas, Milan, Lakatos, Peter Laszlo
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Sprache:eng
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Zusammenfassung: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). 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. 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. NKX2-3 and IRGM are susceptibility loci for IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v16.i41.5233