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©2010 Baishideng Publishing Group Co., Limited. All rights reserved.
NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients
Nora Meggyesi, Lajos S Kiss, Magdalena Koszarska, Martin Bortlik, Dana Duricova, Laszlo Lakatos, Tamas Molnar, Martin Leniček, Libor Vítek, Istvan Altorjay, Maria Papp, Zsolt Tulassay, Pal Miheller, Janos Papp, Attila Tordai, Hajnalka Andrikovics, Milan Lukas, Peter Laszlo Lakatos
Nora Meggyesi, Magdalena Koszarska, Attila Tordai, Hajnalka Andrikovics, Department of Molecular Diagnostics, Hungarian National Blood Transfusion Service, H-1113 Budapest, Hungary
Lajos S Kiss, Janos Papp, Peter Laszlo Lakatos, 1st Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary
Martin Bortlik, Dana Duricova, Milan Lukas, IBD Clinical and Research Centre, ISCARE IVF and 1st Medical Faculty, Charles University, 170 04 Prague, Czech Republic
Laszlo Lakatos, 1st Department of Medicine, Csolnoky F. County Hospital, H8200 Veszprem, Hungary
Tamas Molnar, 1st Department of Medicine, University of Szeged, H6720 Szeged, Hungary
Martin Leniček, Libor Vítek, Department of Biochemistry and Laboratory Diagnostics, 1st Medical Faculty, Charles University, 170 04 Prague, Czech Republic
Istvan Altorjay, Maria Papp, 2nd Department of Medicine, University of Debrecen, H4032 Debrecen, Hungary
Zsolt Tulassay, Pal Miheller, 2nd Department of Medicine, Semmelweis University, H1085 Budapest, Hungary
Author contributions: Meggyesi N, Koszarska M, Tordai A and Andrikovics H carried out genetic analysis and data analysis, collection and validation of patients, and manuscript preparation; Leniček M and Vítek L provided the DNA samples for the Czech patients and controls, and helped with manuscript preparation; Kiss LS, Bortlik M, Duricova D, Lakatos L, Molnar T, Altorjay I, Papp M, Tulassay Z, Miheller P, Papp J and Lukas M performed data collection and manuscript preparation; Lakatos PL was responsible for study design, data collection, data analysis, collection and validation of patients, and manuscript preparation.
Supported by An unrestricted research grant from Abbott Laboratories; an OTKA postdoctoral fellowship (PF63953) (to Andrikovics H); the Bolyai Janos Postdoctoral Scholarship of the Hungarian Academy of Sciences (to Lakatos PL); No. NR/9219-3/2007 of the Internal Grant Agency of the Czech Ministry of Health (to Lukas M); Generation of the Czech IBD as well as control databases was enabled by the support of a grant given by the Czech Ministry of Education No. 2B06155
Correspondence to: Peter Laszlo Lakatos, MD, PhD, 1st Department of Medicine, Semmelweis University, Koranyi st. 2/A, H-1083 Budapest, Hungary.
kislakpet@bel1.sote.hu
Telephone: +36-1-2100278 Fax: +36-1-3130250
Received: July 1, 2010
Revised: August 2, 2010
Accepted: August 9, 2010
Published online: November 7, 2010
AIM: 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.
CONCLUSION: NKX2-3 and IRGM are susceptibility loci for IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.
