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, L. Lakatos, T. Molnár, Martin Leniček, Libor Vítek, I. Altorjay, M. Papp, Z. Tulassay, P. Miheller, J. Papp, A. Tordai, H. Andrikovics, Milan Lukas, P. Lakatos

Research output: Contribution to journalArticle

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Abstract

AIM: To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotypephenotype 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.

Original languageEnglish
Pages (from-to)5233-5240
Number of pages8
JournalWorld Journal of Gastroenterology
Volume16
Issue number41
DOIs
Publication statusPublished - Nov 7 2010

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GTP Phosphohydrolases
Disease Susceptibility
Inflammatory Bowel Diseases
Crohn Disease
Immunity
Ulcerative Colitis
Alleles
Minor Lymphocyte Stimulatory Loci
Skin Manifestations
Azathioprine
Genetic Association Studies
Colon
Steroids
Phenotype
Genes

Keywords

  • Crohn's disease
  • ECM1
  • Genotype
  • Immunity-related GTPase family M
  • NKX2-3
  • Pharmacogenetics
  • Phenotype
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

NKX2-3 AND IRGM variants are associated with disease susceptibility to IBD in Eastern European patients. / Meggyesi, Nora; Kiss, Lajos S.; Koszarska, Magdalena; Bortlik, Martin; Duricova, Dana; Lakatos, L.; Molnár, T.; Leniček, Martin; Vítek, Libor; Altorjay, I.; Papp, M.; Tulassay, Z.; Miheller, P.; Papp, J.; Tordai, A.; Andrikovics, H.; Lukas, Milan; Lakatos, P.

In: World Journal of Gastroenterology, Vol. 16, No. 41, 07.11.2010, p. 5233-5240.

Research output: Contribution to journalArticle

Meggyesi, Nora ; Kiss, Lajos S. ; Koszarska, Magdalena ; Bortlik, Martin ; Duricova, Dana ; Lakatos, L. ; Molnár, T. ; Leniček, Martin ; Vítek, Libor ; Altorjay, I. ; Papp, M. ; Tulassay, Z. ; Miheller, P. ; Papp, J. ; Tordai, A. ; Andrikovics, H. ; Lukas, Milan ; Lakatos, P. / NKX2-3 AND IRGM variants are associated with disease susceptibility to IBD in Eastern European patients. In: World Journal of Gastroenterology. 2010 ; Vol. 16, No. 41. pp. 5233-5240.
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abstract = "AIM: To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotypephenotype 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.",
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T1 - NKX2-3 AND IRGM variants are associated with disease susceptibility to IBD in Eastern European patients

AU - Meggyesi, Nora

AU - Kiss, Lajos S.

AU - Koszarska, Magdalena

AU - Bortlik, Martin

AU - Duricova, Dana

AU - Lakatos, L.

AU - Molnár, T.

AU - Leniček, Martin

AU - Vítek, Libor

AU - Altorjay, I.

AU - Papp, M.

AU - Tulassay, Z.

AU - Miheller, P.

AU - Papp, J.

AU - Tordai, A.

AU - Andrikovics, H.

AU - Lukas, Milan

AU - Lakatos, P.

PY - 2010/11/7

Y1 - 2010/11/7

N2 - AIM: To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotypephenotype 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.

AB - AIM: To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotypephenotype 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.

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KW - ECM1

KW - Genotype

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KW - NKX2-3

KW - Pharmacogenetics

KW - Phenotype

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