Association of BclI polymorphism of the glucocorticoid receptor gene locus with response to glucocorticoids in inflammatory bowel disease

Iudicibus, Sara De; Stocco, Gabriele; Martelossi, Stefano; Drigo, Ilenia; Norbedo, Stefania; Lionetti, Paolo; Pozzi, Elena; Barabino, A.; Decorti, Giuliana; Bartoli, Fiora; Ventura, Alessandro

doi:10.1136/gut.2006.116160

Cited by 50 publications

(51 citation statements)

References 14 publications

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“…Epidemiological evidence, however, for association between MDR1 variants and steroid response in CD have been inconsistent. Two Italian studies 20,24 did not find associations between the C3435T and G2677T/A variants and response to CS in CD. A Slovenian study 16 examined 10 SNPs in the gene and also did not observe associations with any SNP including the C3435T SNP.…”

Section: Discussionmentioning

confidence: 94%

“…Although intimately associated with steroid metabolism, previous studies on whether variations in the MDR1 gene are associated with steroid response, however, have been unclear. 16,20,24,31 Much of the inconsistency is probably related to the examination of few markers in small sample sizes and differing definitions of steroid response. In order to further clarify the role of the MDR1 gene vis-à-vis steroid dependency in children we comprehensively examined variation across the gene in a large cohort of Canadian children who were administered steroids for CD.…”

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confidence: 97%

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

Krupoves

Mack

Seidman

et al. 2011

Inflammatory Bowel Diseases

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Section: Discussionmentioning

confidence: 94%

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confidence: 97%

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

Krupoves

Mack

Seidman

et al. 2011

Inflammatory Bowel Diseases

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“…Conversely, in Crohn's disease, GG genotype was also related with increased response to glucocorticoid treatment (44). It is possible that the BclI polymorphism exerts different influence depending on tissue, disease and ethnicity (44). Since BclI is an intronic polymorphism, it is also possible that its effect on GR activity may occur by selectively acting on repressor or enhancer sites (42).…”

Section: Discussionmentioning

confidence: 99%

“…The GG genotype was also associated with more severe lung damage in cystic fibrosis patients (42) and with Crohn's disease (43), suggesting a possible decrease in glucocorticoid sensitivity. Conversely, in Crohn's disease, GG genotype was also related with increased response to glucocorticoid treatment (44). It is possible that the BclI polymorphism exerts different influence depending on tissue, disease and ethnicity (44).…”

Section: Discussionmentioning

confidence: 99%

NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association

Souza

Martins

Silva-Junior

et al. 2014

Arq Bras Endocrinol Metab

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Objective: The Brazilian population has heterogeneous ethnicity. No previous study evaluated NR3C1 polymorphisms in a Brazilian healthy population. Materials and methods: We assessed NR3C1 polymorphisms in Brazilians of Caucasian, African and Asian ancestry (n = 380). In a subgroup (n = 40), we compared the genotypes to glucocorticoid (GC) sensitivity, which was previously evaluated by plasma (PF) and salivary (SF) cortisol after dexamethasone (DEX) suppression tests, GC receptor binding affinity (K d ), and DEX-50% inhibition (IC 50 ) of concanavalin-A-stimulated mononuclear cell proliferation. p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) allelic discrimination was performed by Real-Time PCR (Polymerase Chain Reaction). Exons 3 to 9 and exon/intron boundaries were amplified by PCR and sequenced. Results: Genotypic frequencies (%) were: rs6195 (n = 380; AA:96.6/AG:3.14/GG:0.26), rs6189-6190 (n = 264; GG:99.6/ GA:0.4), rs41423247 (n = 264; CC:57.9/CG:34.1/GG:8.0), rs6188 (n = 155; GG:69.6/GT:25.7/TT:4.7), rs258751 (n = 150; CC:88.0/CT:10.7/TT:1.3), rs6196 (n = 176; TT:77.2/TC:20.4/CC:2.4), rs67300719 (n = 137; CC:99.3/CT:0.7), and rs72542757 (n = 137; CC:99.3/CG:0.7). The rs67300719 and rs72542757 were found only in Asian descendants, in whom p.N363S and p.ER22/23EK were absent. The p.ER22/23EK was observed exclusively in Caucasian descendants. Hardy-Weinberg equilibrium was observed, except in the Asian for rs6188 and rs258751, and in the African for p.N363S. The K d , IC 50 , baseline and after DEX PF or SF did not differ between genotype groups. However, the mean DEX dose that suppressed PF or SF differed among the BclI genotypes (P = 0.03). DEX dose was higher in GG-(0.7 ± 0.2 mg) compared to GC-(0.47 ± 0.2 mg) and CC-carriers (0.47 ± 0.1 mg). Conclusion: The genotypic frequencies of NR3C1 polymorphisms in Brazilians are similar to worldwide populations. Additionally, the BclI polymorphism was associated with altered pituitary-adrenal axis GC sensitivity. Arq Bras Endocrinol Metab. 2014;58(1):53-61 Keywords NR3C1 genotypes; allelic frequencies; glucocorticoid sensitivity RESUMO Objetivo: Este estudo avalia polimorfismos (SNPs) do NR3C1 na população brasileira, que possui origem étnica heterogênea. Materiais e métodos: SNPs do NR3C1 foram avaliados em brasileiros de ancestralidade caucasiana, africana ou japonesa (n = 380). Em um subgrupo (n = 40), os genótipos foram comparados à sensibilidade aos glicocorticoides (GC), previamente avaliada por cortisol plasmático (PF) e salivar (SF) após supressão com dexametasona (DEX), ensaio de afinidade do receptor ao GC (K d ) e inibição por DEX de 50% da proliferação de mononucleares estimulada por concanavalina-A (IC 50 ). Discriminação alélica de p.N363S (rs6195), p.ER22/23EK (rs6189-6190) e BclI (rs41423247) foi realizada por PCR em tempo real. Éxons 3 a 9 e transições éxon/íntron foram amplificados e sequenciados. Resultados: Frequências genotípicas (%) foram: rs6195 (n = 380; AA:96,6/AG:3,14/GG:0,26), rs6189-6190 (n = 264; GG:99,6/GA:0...

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“…As GCR polymorphisms only modestly alter the phenotype, it is not surprising that the Bcll polymorphism did not affect the phenotype measurably, as other studies have also not demonstrated meaningful associations (39,40,41,42).…”

Section: Discussionmentioning

confidence: 94%

Investigation of glucocorticoid receptor polymorphisms in relation to metabolic parameters in Addison's disease

Ross

Levitt

Merwe

et al. 2013

European Journal of Endocrinology

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Background: Uncertainty exists whether glucocorticoid receptor (GCR) polymorphisms play a role in steroid-related side effects in Addison's disease (AD) patients on hydrocortisone. The polymorphisms Bcll and N363S appear to increase sensitivity to cortisol, while the ER22/23EK polymorphism has been associated with resistance to cortisol. Method: One hundred and forty seven AD patients, and gender, and ethnicity-matched controls were recruited in South Africa. Three polymorphisms in the GCR were studied, using PCR followed by restriction fragment length analysis. Associations with BMI, lipids, glucose and inflammatory markers were investigated. Results: In both patients and controls, the Bcll polymorphism occurred more frequently in whites than in other ethnic groups studied but was not associated with any of the metabolic parameters tested. The ER22/23EK polymorphism was associated with an increased BMI in both patients (29.4 vs 24.7 kg/m

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Association of BclI polymorphism of the glucocorticoid receptor gene locus with response to glucocorticoids in inflammatory bowel disease

Cited by 50 publications

References 14 publications

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

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

NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association

Investigation of glucocorticoid receptor polymorphisms in relation to metabolic parameters in Addison's disease

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