摘要目的 探讨多药耐药基因1(MDR1)、NR3C1基因多态性及临床危险因素与IBD患者糖皮质激素(以下简称激素)疗效、依赖及抵抗的相关性.方法 收集196名健康对照者和105例使用糖皮质激素治疗的IBD患者抗凝血样本.IBD患者中,UC患者62例,CD患者43例.UC患者中激素敏感、依赖、抵抗者分别为36例、13例、13例,CD患者中激素敏感、依赖、抵抗者分别为24例、11例、8例,激素难治包括激素依赖和抵抗.采用限制性片段长度多态性-聚合酶链反应(RFLP-PCR)方法检测所有受试者MDR1 C3435T和NR3C1 Bcl Ⅰ位点的基因型.采用卡方检验或Fisher确切概率法或t检验分析各基因型的频率,以及IBD患者临床特征与患者激素疗效的关系.结果 UC患者中,激素难治组、激素抵抗组较激素敏感组病程长[(6.660±1.523)年,(6.500±1.111)年比(3.350±0.697)年,t=2.211,P=0.031;t=2.930,P=0.005],激素难治组较激素敏感组血清CRP水平高[(47.628±13.913) mg/L比(16.854±4.121) mg/L,t=2.121,P=0.047].与激素敏感的UC组比较,慢性复发型UC在激素难治组更多见(Fisher确切概率法,P=0.035),重度UC在激素抵抗组中较多见(Fisher确切概率法,P=0.021).激素抵抗组、激素难治组的CD患者白细胞计数均较激素敏感组低[(5.710±0.604)×109/L,(5.878±0.405)×109/L比(7.814±0.670)×109/L,t=2.334,P=0.028; t=2.045,P=0.018].与激素敏感组相比,激素抵抗的CD患者中有肠外表现者更多见(Fisher确切概率法,P=0.035).健康对照组与IBD激素敏感组、激素依赖组或激素抵抗组之间,MDR1 C3435T和NR3C1 BclⅠ基因型、等位基因和基因携带频率差异均无统计学意义(P均＞0.05).但在激素敏感组与激素难治组之间,尤其是激素敏感组和激素抵抗组之间,MDR1 C3435T基因携带频率差异有统计学意义(68.33％比48.89％,x2=4.051,P=0.044,68.33％比42.86％,x2=4.274,P=0.039).结论 IBD患者MDR1C3435T位点T基因携带者较非T基因携带患者对激素敏感性高.NR3C1多态性与IBD患者激素依赖与抵抗无关.与激素敏感者相比较,激素依赖与抵抗者中病程长、慢性复发型、重度、血清CRP水平高的UC患者,以及白细胞计数低、有肠外表现的CD患者较为常见.

abstractsObjective To investigate the correlation of multidrug resistance gene 1 (MDR1),NR3C1 gene polymorphisms and clinical risk factors with efficacy,dependence,and resistance of glucocorticoid (GC) in patients with inflammatory bowel disease (IBD).Methods Anti coagulation blood samples of 196 healthy controls and 105 IBD patients received GC therapy were collected.There were 62 ulcerative colitis (UC) and 43 Crohn's disease (CD) in the IBD patients.The number of GC sensitive,GC dependent and GC resistant of UC patients were 36,13 and 13,respectively,and those of CD patients were 24,11 and eight.GC refractoriness included GC dependence and resistance.The genotype of MDR1 C3435T and NR3C1 Bcl Ⅰ of all the subjects was detected by the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR).The correlation between each genotype frequency,clinical features of patients with IBD and the efficacy of GC treatment was analyzed by Chisquare test,Fisher exact probability method or t test.Results Among UC patients,the disease course of GC refractory group and GC resistant group was longer than that of GC sensitive group ((6.660±1.523)years,(6.500±1.111) yearsvs (3.350±0.697) years,t=2.211,P=0.031; t=2.930,P=0.005).The serum level of C reaction protein (CRP) of GC refractory group was higher than that of GC sensitive group ((47.628±13.913) mg/Lvs (16.854±4.121) mg/L,t=2.121,P=0.047).The chronic relapse type was more common in GC refractory UC patients (Fisher exact probability method,P=0.035),and severe patients were more common in UC with GC resistance (Fisher exact probability method,P=0.021).The white blood cell count of GC resistant and GC refractory CD patient was lower than that of GC sensitive CD patients ((5.710 ± 0.604) ×109/L,(5.878±0.405) × 109/L vs (7.814 ±0.670) × 109/L,t=2.334,P=0.028; t=2.045,P=0.018).Patients with extraqntestinal manifestations was more common in CD with GC resistance (Fisher exact probability method,P=0.035).There was no statistically significant difference in the frequencies of MDR1 C3435T,NR3C1 Bcl Ⅰ genotypes,allelic genes and gene carrier among control group and GC sensitive dependent and resistant group of IBD patients.However,the frequency of MDR1 C3435T gene carrier was significantly different between GC sensitive group and GC refractory group,especially between GC sensitive group and GC resistance group (68.33％ vs 48.89％,x2 =4.051,P=0.044; 68.33％ vs 42.86％,x2 =4.274,P =0.039).Conclusions GC sensitivity of IBD patients with MDR1 C3435T loci T gene carrier was higher than that of IBD patients without T gene carrier.NR3C1 gene polymorphisms was not related with GC resistance and GC dependence.Compared with GC sensitive IBD patients,in GC resistant and GC dependent IBD pantient UC patients with long disease course,chronic relapse type,severe type,high level of CRP and CD patients with low white blood cell count and extra-intestinal manifestations were more common.