多药耐药基因及临床危险因素与炎症性肠病患者激素治疗应答的关系
다약내약기인급림상위험인소여염증성장병환자격소치료응답적관계
Correlation of multidrug resistance genes and clinical risk factors with glucocorticoid response in patients with inflammatory bowel disease
  • 万方数据
    中华消化杂志 중화소화잡지
    Chinese Journal of Digestion
    2014年 12期 817-822 ,共6页

    刘露%马雅琼%胡佳辰%周瑞%李瑾%黄梅芳%夏冰

    류로%마아경%호가신%주서%리근%황매방%하빙

    炎性肠疾病%多药耐药基因基因%受体,糖皮质激素%多态现象,遗传 炎性腸疾病%多藥耐藥基因基因%受體,糖皮質激素%多態現象,遺傳
    염성장질병%다약내약기인기인%수체,당피질격소%다태현상,유전
    Inflammatory bowel diseases%MDR1 gene%Receptors,glucocorticoid%Polymorphism,genetic
    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.
    목적 탐토다약내약기인1(MDR1)、NR3C1기인다태성급림상위험인소여IBD환자당피질격소(이하간칭격소)료효、의뢰급저항적상관성.방법 수집196명건강대조자화105례사용당피질격소치료적IBD환자항응혈양본.IBD환자중,UC환자62례,CD환자43례.UC환자중격소민감、의뢰、저항자분별위36례、13례、13례,CD환자중격소민감、의뢰、저항자분별위24례、11례、8례,격소난치포괄격소의뢰화저항.채용한제성편단장도다태성-취합매련반응(RFLP-PCR)방법검측소유수시자MDR1 C3435T화NR3C1 Bcl Ⅰ위점적기인형.채용잡방검험혹Fisher학절개솔법혹t검험분석각기인형적빈솔,이급IBD환자림상특정여환자격소료효적관계.결과 UC환자중,격소난치조、격소저항조교격소민감조병정장[(6.660±1.523)년,(6.500±1.111)년비(3.350±0.697)년,t=2.211,P=0.031;t=2.930,P=0.005],격소난치조교격소민감조혈청CRP수평고[(47.628±13.913) mg/L비(16.854±4.121) mg/L,t=2.121,P=0.047].여격소민감적UC조비교,만성복발형UC재격소난치조경다견(Fisher학절개솔법,P=0.035),중도UC재격소저항조중교다견(Fisher학절개솔법,P=0.021).격소저항조、격소난치조적CD환자백세포계수균교격소민감조저[(5.710±0.604)×109/L,(5.878±0.405)×109/L비(7.814±0.670)×109/L,t=2.334,P=0.028; t=2.045,P=0.018].여격소민감조상비,격소저항적CD환자중유장외표현자경다견(Fisher학절개솔법,P=0.035).건강대조조여IBD격소민감조、격소의뢰조혹격소저항조지간,MDR1 C3435T화NR3C1 BclⅠ기인형、등위기인화기인휴대빈솔차이균무통계학의의(P균＞0.05).단재격소민감조여격소난치조지간,우기시격소민감조화격소저항조지간,MDR1 C3435T기인휴대빈솔차이유통계학의의(68.33％비48.89％,x2=4.051,P=0.044,68.33％비42.86％,x2=4.274,P=0.039).결론 IBD환자MDR1C3435T위점T기인휴대자교비T기인휴대환자대격소민감성고.NR3C1다태성여IBD환자격소의뢰여저항무관.여격소민감자상비교,격소의뢰여저항자중병정장、만성복발형、중도、혈청CRP수평고적UC환자,이급백세포계수저、유장외표현적CD환자교위상견.
    Objective 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.
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