The predictive value of intestinal α4β7 integrin gene polymorphism in patients with ulcerative colitis

Zhilin I.V.; Chashkova E.Yu.; Zhilina A.A.; Markovskiy A.V.

doi:https://doi.org/10.17116/dokgastro20211003115

Zhilin I.V.

Irkutsk Scientific Centre of Surgery and Traumatology;
Chita State Medical Academy

Chashkova E.Yu.

Irkutsk Scientific Centre of Surgery and Traumatology

Zhilina A.A.

Chita State Medical Academy

Markovskiy A.V.

Chita State Medical Academy

The predictive value of intestinal α4β7 integrin gene polymorphism in patients with ulcerative colitis

Authors:

Zhilin I.V., Chashkova E.Yu., Zhilina A.A., Markovskiy A.V.

More about the authors

Journal: Russian Journal of Evidence-Based Gastroenterology. 2021;10(3): 15‑20

DOI: 10.17116/dokgastro20211003115

Read: 1201 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Zhilin IV, Chashkova EYu, Zhilina AA, Markovskiy AV. The predictive value of intestinal α4β7 integrin gene polymorphism in patients with ulcerative colitis. Russian Journal of Evidence-Based Gastroenterology. 2021;10(3):15‑20. (In Russ.)
https://doi.org/10.17116/dokgastro20211003115

Подписка 2026 Доказательная гастроэнтерология (Russian Journal of Evidence-Based Gastroenterology)

Использование инфографики авторами научных работ

Close metadata

OBJECTIVE

We assessed genes ITGA4 (rs1143674; rs1449263) and ITGB7 (rs11574532) polymorphisms as possible predictors for surgical treatment in patients with ulcerative colitis (UC).

MATERIAL AND METHODS

A retrospective study from 2017 to 2020 included 86 patients (27 — the surgical treatment group; 59 — the conservative treatment group) and 115 healthy volunteers (control group) born and living in the Irkutsk region and the Trans-Baikal Territory. Genotypes were studied by the polymerase chain reaction in real-time. The χ² test, odds ratio, and binary logistic regression analysis were used for statistical analysis in the IBM SPSS Statistics Version 25.0 program.

RESULTS

Homozygotes GG ITGA4 (rs1449263) in the conservative treatment group were found 2.6 times more often than in control group (p=0.017; OR=2.663 CI 95%; 1.164—6.090), the distribution frequency of ITGA4 (rs1143674) and ITGB7 (rs11574532) did not differ in these groups (p>0.05). In patients heterozygous for the ITGA4 (rs1449263) AG gene, indications for surgery were found 3.4 times more often than in homozygous patients (p=0.026; OR=3.4; 95% CI: 1.113—10 582). Carriers of ITGB7 (rs11574532) TT were found only in the surgical treatment group (p=0.018). In patients with proctitis, there were no indications for coloproctectomy (p=0.037), with pancolitis, the chances of surgery increased 6.7 times (p=0.007; OR=6.7; 95% CI; 1.454—30.577). Regression logistic analysis revealed that ITGB7 (rs11574532) (p=0.04; 95% CI 1.037—11.162) and UC oncet age (p=0.009; 95% CI: 1.581—23.437) were predictors of the coloproctectomy, which were included into the logistic regression equation.

CONCLUSION

Polymorphisms ITGA4 (rs1449263) AG, ITGB7 (rs11574532) TT combined with factors as early onset of UC and pancolitis are predictors of coloproctectomy. According to the ROC-curve data, the developed model has a good predictive power (AUC=0.807, 95% CI 0.729—0.886, p<0.001; standard error 0.04).

Keywords:

ulcerative colitis

coloproctectomy

integrin

coloproctectomy predictors

ITGA4 (rs1143674)

ITGA4 (rs1449263)

ITGB7 (rs11574532)

Authors:

Zhilin I.V.

Irkutsk Scientific Centre of Surgery and Traumatology;
Chita State Medical Academy

Chashkova E.Yu.

Irkutsk Scientific Centre of Surgery and Traumatology

Zhilina A.A.

Chita State Medical Academy

Markovskiy A.V.

Chita State Medical Academy

Received:

22.08.2021

Accepted:

07.09.2021

Close metadata

References:

Jazvennyj kolit. Klinicheskie rekomendacii. 2020. Accessed July 04, 2021. (In Russ.). https://www.consultant.ru/document/cons_doc_LAW_358274/8efd5f17af55cb35a770f73937590c642437b7eb
Lord JD, Long SA, Shows DM, Thorpe J, Schwedhelm K, Chen J, Kita M, Buckner JH. Circulating integrin alpha4/beta7+ lymphocytes targeted by vedolizumab have a pro-inflammatory phenotype. Clinical Immunology Society. 2018;193:24-32. https://doi.org/10.1016/j.clim.2018.05.006
Kim J, Yoon H, Kim N, Lee KM, Jung SA, Choi CH, Kim ES, Jung Y, Eun CS, Kim TO, Kang SB, Kim YS, Seo GS, Lee CK, Im JP, Park SJ, Park DI, Ye BD. Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients with Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study. Inflammatory Bowel Diseases. 2021;izaa361. https://doi.org/10.1093/ibd/izaa361
Achkasov SI, Shapina MV, Veselov VV, Vardanjan AV, Mingazov AF, Ponomarenko AA. Predictors of coloprotectomy in patients with severe ulcerative colitis. Koloproktologija. 2020;19(3):37-48. (In Russ.). https://doi.org/10.33878/2073-7556-2020-19-3-37-48
Lang TA, Altman DG. Basic statistical reporting for articles published in biomedical journals: the «Statistical Analyses and Methods in the Published Literature» or the SAMPL Guidelines. International Journal of Nursing Studies Advances. 2015;52(1):5-9. https://doi.org/10.1016/j.ijnurstu.2014.09.006
Mudrov VA. Cluster analysis algorithms in biomedical research using the SPSS software package. Zabajkal’skij Medicinskij Vestnik. 2020;4:215-221. (In Russ.).
Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, Caprilli R, Colombel JF, Gasche C, Geboes K, Jewell DP, Karban A, Loftus EJ, Peña AS, Riddell RH, Sachar DB, Schreiber S, Steinhart AH, Targan SR, Vermeire S, Warren BF. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Canadian Journal of Gastroenterology. 2005;19(suppl A):5-36. https://doi.org/10.1155/2005/269076
Eriksson C, Cao Y, Rundquist S, Zhulina Y, Henriksson I, Montgomery S, Halfvarson J. Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Örebro, Sweden, 1963—2010. Alimentary Pharmacology and Therapeutics. 2017; 46(8):748-757. https://doi.org/10.1111/apt.14268
Mudrov VA. Statistical analysis algorithms of qualitative features in biomedical research using the SPSS software package. Zabajkal’skij Medicinskij Vestnik. 2020;1:151-163. (In Russ.).
Mudrov VA. Regression analysis algorithms in biomedical research using the SPSS software package. Zabajkal’skij medicinskij vestnik. 2020;2:177-190. (In Russ.).
Pan L, Zhao Y, Yuan Z, Qin G. Research advances on structure and biological functions of integrins. SpringerPlus. 2016;5(1):1094. https://doi.org/10.1186/s40064-016-2502-0
Liu S, Rose DM, Han J, Ginsberg MH. Alpha4 integrins in cardiovascular development and diseases. Trends in Cardiovascular Medicine. 2000;10(6):253-257. https://doi.org/10.1016/s1050-1738(00)00073-6
Goncharova IA, Nazarenko MS, Babushkina NP, Markov AV, Pecherina TB, Kashtalap VV, Tarasenko NV, Ponasenko AV, Barbarash OL, Puzyrev VP. Genetic predisposition to early myocardial infarction. Molekulyarnaya biologiya. 2020;54(2):224-232. (In Russ.). https://doi.org/10.31857/S002689842002004
Correia C, Coutinho AM, Almeida J, Lontro R, Lobo C, Miguel TS, Martins M, Gallagher L, Conroy J, Gill M, Oliveira G, Vicente AM. Association of the alpha4 integrin subunit gene (ITGA4) with autism. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 2009;150B(8):1147-1151. https://doi.org/10.1002/ajmg.b.30940
Etzioni A, Doerschuk CM, Harlan JM. Of man and mouse: leukocyte and endothelial adhesion molecule deficiencies. Blood. 1999;94(10):3281-3288.
van Heel DA, Carey AH, Jewell DP. Identification of novel polymorphisms in the beta7 integrin gene: family-based association studies in inflammatory bowel disease. Genes and Immunity. 2001;2(8):455-60. https://doi.org/10.1038/sj.gene.6363810