Clinical and Experimental Medicine

, Volume 19, Issue 3, pp 367–375 | Cite as

Functional polymorphisms of the receptor for the advanced glycation end product promoter gene in inflammatory bowel disease: a case–control study

  • Rachele CiccocioppoEmail author
  • Sara Bozzini
  • Elena Betti
  • Venerina Imbesi
  • Catherine Klersy
  • Lucia Sukovska LakyovaEmail author
  • Lukas Sukovsky
  • Jozef Benacka
  • Peter KruzliakEmail author
  • Gino Roberto Corazza
  • Antonio Di Sabatino
  • Colomba Falcone
Original Article


The receptor for the advanced glycation end products (RAGE) is a multiligand transmembrane receptor involved in chronic inflammation whose specific polymorphisms of the promoter gene were found to increase its transcriptional activity. We investigated the association of both allelic and genotypic -374T/A and -429T/C polymorphisms with inflammatory bowel disease. The STREGA guidelines were applied for planning and reporting. We enrolled 133 patients with Crohn’s disease (CD), 149 with ulcerative colitis (UC), and 128 blood donors. Genomic DNA was extracted from peripheral blood leukocytes collected from each patient and control. RAGE polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. The Hardy–Weinberg equilibrium was first assessed, and then, the Kruskal–Wallis test and the Fisher exact test were used for etiologic group comparisons. Distribution of patients’ characteristics across genotypes was evaluated by the Fisher exact test, while that across alleles was analyzed with a probit model. A 2-sided value of p < 0.05 was considered significant. Following the evidence of the Hardy–Weinberg equilibrium, we found a higher prevalence of the allele A of the -374T/A haplotype in UC (p = 0.043), and of the allele C of the -429T/C haplotype in CD (p < 0.001) with respect to the other groups. Moreover, the homozygous AA genotype of the -374T/A polymorphism resulted associated with late onset of CD, while its TT genotype with early onset (p = 0.049). The allele C of the 429T/C haplotype was associated with early onset of UC (p = 0.03), while a higher frequency of the heterozygous TC haplotype was found in those with pancolitis (p = 0.026). The differing distribution of these polymorphisms in healthy donors and CD/UC patients suggests a role in the development and outcome of these pathological conditions.


Gene polymorphisms Inflammatory bowel disease RAGE 



Crohn’s disease


Clinical activity index


Crohn’s disease activity index


Inflammatory bowel diseases


Receptor for the advanced glycation end products


Ulcerative colitis



This study was funded by a grant from: Direzione Scientifica, Fondazione I.R.C.C.S. Policlinico San Matteo (Pavia, Italy) – Progetto di Ricerca Corrente entitled: “STUDIO DELLA ESPRESSIONE DEL RECETTORE PER I PRODOTTI FINALI DELLA GLICOSILAZIONE AVANZATA (RAGE) NELLE MALATTIE INFIAMMATORIE CRONICHE INTESTINALI” to R.C. The Direzione Scientifica did not take part in the study design, collection, analysis and interpretation of data, writing the manuscript, and decision to submit the paper for publication. The authors are grateful to Mrs. Sheila McVeigh for her thorough revision of the English text.

Compliance with ethical standards

Conflict of interest

Dr. Ciccocioppo received a consulting (honorary) fee by Takeda Pharmaceuticals, and she is a member of the Advisory Board Takeda Italy. All the other authors of this manuscript have no conflict of interest to disclose.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Gastroenterology Unit, Department of MedicineAOUI Policlinico G.B. Rossi and University of VeronaVeronaItaly
  2. 2.Interdipartimental Center for the Molecular Medicine Research and Cardiology UnitIstituto di Cura Città di Pavia and University of PaviaPaviaItaly
  3. 3.Clinica Medica I, Department of Internal Medicine and TherapeuticsI.R.C.C.S. Policlinico San Matteo Foundation and University of PaviaPaviaItaly
  4. 4.Gastroenterology and Digestive Endoscopy UnitLegnano Hospital, ASST Ovest MilaneseLegnanoItaly
  5. 5.Service of Clinical Epidemiology and BiostatisticsFondazione I.R.C.C.S. Policlinico San MatteoPaviaItaly
  6. 6.1st Department of Surgery, Faculty of MedicinePavol Jozef Safarik University and Louis Pasteur University HospitalKosiceSlovakia
  7. 7.Faculty of Health and Social WorkTrnava UniversityTrnavaSlovakia
  8. 8.Department of Internal MedicineBrothers of Mercy HospitalBrnoCzech Republic
  9. 9.2nd Department of Surgery, Faculty of MedicineMasaryk University and St. Anne’s University HospitalBrnoCzech Republic

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