Molecular and genetic diagnostics of inflammatory bowel diseases

Cover Page


Cite item

Full Text

Abstract

Background: In the last two decades, more attention  has  been   paid  to  the   development and implementation of molecular and genetic technologies  for  the   diagnosis   and   prediction of the  development and  course  of inflammatory bowel diseases (IBD). However, the published evidence   on   their   diagnostic   significance   are rather   controversial   and   equivocal   that   may be explained by some characteristics of their frequencies, differences  in pathogenetic, clinical and diagnostic vales of the genetic polymorphisms in various countries and regions.

Aim: To evaluate the frequency, clinical, diagnostic, and prognostic significance  of  the  3020insC  and  G2722С nucleotide  polymorphisms  of the CARD15 (NOD2) gene  in Crohn's disease (CD) and ulcerative colitis (UC) in  the   Kemerovo  Region  of  the   Russian Federation.

Materials and methods:  The study included 144 patients with IBD (58 with CD, 86 with UC), and 44 patients  without  any gastrointestinal tract disorders in the control group. The 3020insC and 2722С allelic frequencies  of the CARD15 gene were determined. All patients  were of the Russian ethnicity  and  were  living in the  territory  of the Kemerovo Region at the time of the study.

Results: The frequency of the 3020insC allele of the CARD15 gene  in CD patients  was significantly higher than in those with UC (16% vs 3%, p < 0.001) and in the control  group   (5%,  р = 0.04).  The  homozygous genotype of 3020insC/insC was found only in the CD patients. The carriage  of the  3020insC allele was associated  with an average  3.5-fold increase of the probability of CD development (odds ratio [OR] 3.6;  95% confidential  interval  [CI]:  1.3–10.3) and was not significantly linked to an increased risk of UC (OR 0.6; 95% CI: 0.1–2.5). The 3020insC allelic frequency in the pooled group of the patients with complicated  CD variants (with stricture formation and  penetrative)  was  significantly  higher, compared to those with the luminal forms (79% vs 21%, р = 0.03) and with the penetrative CD forms compared to  the  luminal (50% vs 21%, р = 0.05). The 3020insC allele carriage in the CD patients was associated with a 3.3-fold increase in the risk of the penetrative forms of the disease  (OR 3.3; 95% CI: 1.8–6.1) and with a 14-fold increase of the overall risk of the complicated  CD variants (OR 14.1; 95% CI: 7.1–27.9). The 2722С allelic frequency in CD and UC patients  and  in the  control  group  were  not significantly different.

Conclusion: The detection of the  3020insC allele of the  CARD15 gene  in the Kemerovo Region of the Russian Federation is appropriate for the early CD diagnosis, assessment of the prognosis for the risk of development of CD phenotypic variants, as well as for the differential diagnosis between CD and UC.

About the authors

D. A. Kuznetsova

Kemerovo State Medical University; Kemerovo Regional Clinical Hospital

Author for correspondence.
Email: lariwar@mail.ru

Kuznetsova Daria A. – MD, Postgraduate Student, Сhair of Pathophysiology, Medical and Clinical Biochemistry KSMU, Doctor of Immunology Laboratory KRCH.

22 Oktyabr'skiy prospekt, Kemerovo, 650066, +7 (923) 497 21 10.

Россия

A. S. Razumov

Kemerovo State Medical University

Email: fake@neicon.ru

Razumov Aleksandr S. – MD, PhD, Professor, Сhair of Pathophysiology, Medical and Clinical Biochemistry.

22a Voroshilova ul., Kemerovo, 650029

Россия

M. V. Merzlyakov

Kemerovo Regional Clinical Hospital

Email: fake@neicon.ru

Merzlyakov Mikhail V. – MD, PhD, Head of the Department of Endoscopy.

22 Oktyabr'skiy prospekt, Kemerovo, 650066

Россия

G. V. Vavin

Kemerovo Regional Clinical Hospital

Email: fake@neicon.ru

Vavin Grigoriy V. – MD, PhD, Deputy Head Physician on Laboratory Diagnostics.

22 Oktyabr'skiy prospekt, Kemerovo, 650066

Россия

R. V. Repnikova

Kemerovo State Medical University

Email: fake@neicon.ru

Repnikova Renata V. – MD, PhD, Professor, Chair of Therapy, Occupational Pathology and Endocrinology.

22a Voroshilova ul., Kemerovo, 650029

Россия

References

  1. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015;12(12):720–7. doi: 10.1038/nrgastro.2015.150.
  2. Tontini GE, Vecchi M, Pastorelli L, Neurath MF, Neumann H. Differential diagnosis in inflammatory bowel disease colitis: state of the art and future perspectives. World J Gastroenterol. 2015;21(1):21–46. doi: 10.3748/wjg.v21.i1.21.
  3. Lee JM, Lee KM. Endoscopic diagnosis and differentiation of inflammatory bowel disease. Clin Endosc. 2016;49(4):370–5. doi: 10.5946/ce.2016.090.
  4. Magro F, Langner C, Driessen A, Ensari A, Geboes K, Mantzaris GJ, Villanacci V, Becheanu G, Borralho Nunes P, Cathomas G, Fries W, Jouret-Mourin A, Mescoli C, de Petris G, Rubio CA, Shepherd NA, Vieth M, Eliakim R; European Society of Pathology (ESP); European Crohn's and Colitis Organisation (ECCO). European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis. 2013;7(10):827–51. doi: 10.1016/j.crohns.2013.06.001.
  5. Mokhtarifar A, Ganji A, Sadrneshin M, Bahari A, Esmaeilzadeh A, Ghafarzadegan K, Nikpour S. Diagnostic Value of ASCA and atypical p-ANCA in differential diagnosis of inflammatory bowel disease. Middle East J Dig Dis. 2013;5(2):93–7.
  6. Savige J, Gillis D, Benson E, Davies D, Esnault V, Falk RJ, Hagen EC, Jayne D, Jennette JC, Paspaliaris B, Pollock W, Pusey C, Savage CO, Silvestrini R, van der Woude F, Wieslander J, Wiik A. International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA). Am J Clin Pathol. 1999;111(4):507–13.
  7. Liu TC, Stappenbeck TS. Genetics and pathogenesis of inflammatory bowel disease. Annu Rev Pathol. 2016;11:127–48. doi: 10.1146/annurev-pathol-012615-044152.
  8. Ahmad T, Armuzzi A, Bunce M, Mulcahy-Hawes K, Marshall SE, Orchard TR, Crawshaw J, Large O, de Silva A, Cook JT, Barnardo M, Cullen S, Welsh KI, Jewell DP. The molecular classification of the clinical manifestations of Crohn's disease. Gastroenterology. 2002;122(4):854–66. doi: https://doi.org/10.1053/gast.2002.32413.
  9. Nasir BF, Griffiths LR, Nasir A, Roberts R, Barclay M, Gearry RB, Lea RA. An envirogenomic signature is associated with risk of IBD-related surgery in a population-based Crohn's disease cohort. J Gastrointest Surg. 2013;17(9):1643–50. doi: 10.1007/s11605-013-2250-1.
  10. Serbati N, Badre W, Diakite B, Nadifi S. NOD2/CARD15 gene influences disease behavior but not IBD susceptibility in a Moroccan population. Turk J Gastroenterol. 2014;25 Suppl 1:122–8. doi: 10.5152/tjg.2014.3870.
  11. Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, Peyrin-Biroulet L, Cullen GJ, Daperno M, Kucharzik T, Rieder F, Almer S, Armuzzi A, Harbord M, Langhorst J, Sans M, Chowers Y, Fiorino G, Juillerat P, Mantzaris GJ, Rizzello F, Vavricka S, Gionchetti P; ECCO. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1: Diagnosis and Medical Management. J Crohns Colitis. 2017;11(1):3–25.
  12. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F; European Crohn's and Colitis Organisation [ECCO]. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis. 2017;11(6):649–70. doi: 10.1093/ecco-jcc/jjx008.
  13. Sandborn WJ. Crohn's disease evaluation and treatment: clinical decision tool. Gastroenterology. 2014;147(3):702–5. doi: 10.1053/j.gastro.2014.07.022.
  14. Dassopoulos T, Cohen RD, Scherl EJ, Schwartz RM, Kosinski L, Regueiro MD. Ulcerative colitis care pathway. Gastroenterology. 2015;149(1):238–45. doi: 10.1053/j.gastro.2015.05.036.
  15. Pugazhendhi S, Santhanam S, Venkataraman J, Creveaux I, Ramakrishna BS. NOD2 gene mutations associate weakly with ulcerative colitis but not with Crohn's disease in Indian patients with inflammatory bowel disease. Gene. 2013;512(2):309–13. doi: 10.1016/j.gene.2012.10.015.
  16. Guo QS, Xia B, Jiang Y, Qu Y, Li J. NOD2 3020insC frameshift mutation is not associated with inflammatory bowel disease in Chinese patients of Han nationality. World J Gastroenterol. 2004;10(7):1069–71. doi: 10.3748/wjg.v10.i7.1069.
  17. Kim ES, Kim WH. Inflammatory bowel disease in Korea: epidemiological, genomic, clinical, and therapeutic characteristics. Gut Liver. 2010;4(1): 1–14. doi: 10.5009/gnl.2010.4.1.1.
  18. Лоранская ИД, Степанова ЕВ, Халиф ИЛ, Михайлова ТЛ, Щагина ОА, Кадникова ВА, Поляков АВ. Клинико-генетическая ассоциация болезни Крона и полиморфных вариантов гена NOD2/CARD15. Медицинская генетика. 2008;7(9):40–4.
  19. Насыхова ЮА, Семенов НВ, Харитонов АГ, Иващенко ТЭ, Барановский АЮ, Баранов BC. Анализ полиморфизма генов NOD2/ CARD15 и TNF-a у пациентов с хроническими воспалительными заболеваниями желудочно-кишечного тракта. Молекулярная медицина. 2010;(3):32–7.
  20. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001;411(6837):599–603. doi: 10.1038/35079107.
  21. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nuñez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001;411(6837):603–6. doi: 10.1038/35079114.
  22. Biswas A, Petnicki-Ocwieja T, Kobayashi KS. Nod2: a key regulator linking microbiota to intestinal mucosal immunity. J Mol Med (Berl). 2012;90(1):15–24. doi: 10.1007/s00109-011-0802-y.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2017 Kuznetsova D.A., Razumov A.S., Merzlyakov M.V., Vavin G.V., Repnikova R.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies