Associations between variants in the ABCB1 (MDR1) gene and corticosteroid dependence in children with Crohnʼs disease

Krupoves, Alfreda; Mack, David; Seidman, Ernest G.; Deslandres, Colette; Amre, Devendra

doi:10.1002/ibd.21608

Cited by 22 publications

(15 citation statements)

References 57 publications

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“…In the present study, we report positive associations between the C3435T polymorphism and both the chronic use of steroids and disease activity in CD patients. Similar to our results, an association between MDR1 variants and corticosteroid dependence was also reported in children with CD in Canadian tertiary centers (37). In a British study on IBD, the 2677T allele was increased in UC cases, and the TT genotype was strongly associated with disease severity and the use of steroids in UC (27).…”

Section: Discussionsupporting

confidence: 91%

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

Carvalho¹,

Fróes²,

Esberard³

et al. 2014

Clinics

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OBJECTIVES:Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro.METHODS:We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations.RESULTS:No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009), whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories.CONCLUSION:The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut-microbiota interactions and in mediating fibrosis. Understanding the effects of several drugs associated with multidrug resistance 1 gene variants may aid in the selection of customized therapeutic regimens.

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Section: Discussionsupporting

confidence: 91%

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

Carvalho¹,

Fróes²,

Esberard³

et al. 2014

Clinics

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“…We have found no connection between the method of GC therapy and response to it. The GC drugs used in our studies were similar to those investigated in earlier pharmacogenetic research on patients with IBD conducted by Krupoves et al, who evaluated prednisolone and budesonide [24,25]. Gender also showed no effect on the response to the GCs, but we did identify a significant difference in treatment between patients with CD and UC.…”

Section: Discussionsupporting

confidence: 76%

NGS study of glucocorticoids response genes in inflammatory bowel disease patients

et al. 2021

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Introduction: Despite intensive research and a long history of glucocorticoids being applied in various clinical areas, they still generate a challenge for personalized medicine by causing resistance or dependence in nearly 50% of patients treated. The objective of the present study was to determine the genetic predictors of variable reactions in inflammatory bowel disease patients to glucocorticoid therapy. Therefore, based on the current knowledge on how glucocorticoids act, we have compiled a panel of 21 genes for variant analysis: NR3C1,

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“…The wild genotype CC of rs1128503 (C1236T) and rs1045642 (C3435T) should be regarded as risk factors for GC‐dependence in the Chinese CD population. In a previous study, Krupoves et al . included 260 pediatric CD patients and found that rs1045642 (C3435T) was not correlated with GC sensitivity.…”

Section: Discussionmentioning

confidence: 79%

Contribution of MDR1 gene polymorphisms on IBD predisposition and response to glucocorticoids in IBD in a Chinese population

Yang

Chen

Zhang

et al. 2015

J of Digest Diseases

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Associations between variants in the ABCB1 (MDR1) gene and corticosteroid dependence in children with Crohnʼs disease

Abstract: Our results suggest that the ABCB1 gene may be associated with CS dependence in pediatric CD patients.

Cited by 22 publications

References 57 publications

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

NGS study of glucocorticoids response genes in inflammatory bowel disease patients

Contribution of MDR1 gene polymorphisms on IBD predisposition and response to glucocorticoids in IBD in a Chinese population

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