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P416. MDR1 C3435 gene polymorphism and several clinical risk factors associated with glucocorticoid dependence and resistance in inflammatory bowel disease

L. Liu, R. Zhou, B. Xia, Zhongnan Hospital of Wuhan University School of Medicine, Gastroenterology, Wuhan, China

Background

To investigate whether the Multidrug resistance (MDR1) and Glucocorticoid receptor (NR3C1) gene polymorphisms and clinical risks were associated with glucocorticoid (GC) dependence and resistance in patients with inflammatory bowel disease (IBD).

Methods

Of 105 IBD patients (male 55, female 50) who accepted GC therapy (41 intravenous infusion of hydrocortisone with mean dose of 4.380±1.103 mg/kg, 64 oral taking prednisone with mean dose of 0.670±0.297 mg/kg), UC 62, mean age 36.13±12.54ys, ratio of GC efficacy, dependence and resistance is 57.14%, 20.97%, 20.97%, respectively; CD 43, mean age 27.88±13.22ys, ratio of GC efficacy, dependence and resistance is 55.81%, 25.58%, 18.60%, respectively. 196 healthy controls matched with age and gender were enrolled in this study. The SNP C3435T in MDR1 and BclI in NR3C1 were genotyped using RFLP-PCR. Associations between genotype frequencies, clinical risks were analyzed for GC dependence and resistance.

Results

There were no statistical differences in the frequencies of MDR1 C3435T and NR3C1 BclI genotypes between IBD patients with GC dependence and resistance and healthy controls. However, the frequency of MDR1 3435T gene carriers were lower in IBD patients with GC dependence and resistance than in with GC efficacy, especially lower in patients with GC resistance (68.33% vs 48.89%, P = 0.044, 68.33% vs 42.86%, P = 0.039, respectively). In clinical data, long course of disease, chronic relapse type, severe disease and high level of CRP had an important impact on GC therapy outcome (P = 0.031, P = 0.035, P = 0.048, P = 0.047) in UC patients, Especially long course of disease, severe disease in UC patients with GC resistance (P = 0.005, P = 0.021). Low level of WBC was associated with CD in GC dependence (P = 0.05) and resistance (P = 0.028), Extra-intestinal manifestations were associated with CD in GC resistance (P = 0.035).

Conclusion

The MDR1 3435T gene carrier was negatively associated with IBD patients with GC dependence and resistance. Early onset of age, long course, severe activity and high level of CRP were associated with UC, and low level of WBC and extra-intestinal manifestations were associated with CD in GC dependence and resistance.