Interleukin-1 receptor antagonist VNTR-polymorphism in inflammatory bowel disease

被引:27
作者
Vijgen, L
Van Gysel, M
Rector, A
Thoelen, I
Esters, N
Ceelen, T
Vangoidsenhoven, E
Vermeire, S
Rutgeerts, P
Van Ranst, M
机构
[1] Rega Inst, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol, BE-3000 Louvain, Belgium
[2] Univ Hosp Gasthuisberg, Dept Gastroenterol, Louvain, Belgium
关键词
inflammatory bowel disease; Crohn's disease; ulcerative colitis; interleukin-1; interleukin-1 receptor antagonist;
D O I
10.1038/sj.gene.6363888
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Both genetic and environmental factors have been implicated in the etiology of inflammatory bowel diseases (IBD) i.e., Crohn's disease (CD) and ulcerative colitis (UC). Polymorphisms in cytokine genes are likely to influence an individual's predisposition to IBD. In intron 2 of the interleukin-1 receptor antagonist (IL-1ra) gene, a variable number of an 86-bp tandem repeat (VNTR) polymorphism leads to the existence of five different alleles. In order to analyze the association between certain IL-1ra VNTR-alleles and IBD, we investigated the IL-1ra genotype and allele frequencies in 342 unrelated IBD patients and in 401 healthy control individuals. CD patients were also genotyped for the three main associated variants in the NOD2/CARD15 gene. In the IBD group, a significant decrease in the frequency of IL-1ra allele 1 (P = 0. 048) compared to controls was observed. The frequency of IL-1ra genotype 1/1 was significantly lower in the IBD population vs the control group (P = 0.018), Analysis of the CD population without NOD2 homozygotes and compound heterozygotes revealed a more significant decrease in IL-1ra genotype 1/1 compared to controls (P= 0.038). These results support the hypothesis that the IL-1ra VNTR-polymorphism could be among the genetic factors that are of importance in IBD susceptibility.
引用
收藏
页码:400 / 406
页数:7
相关论文
共 38 条
[1]   Inflammatory bowel disease approaching the 3rd millennium: pathogenesis and therapeutic implications? [J].
Ardizzone, S ;
Bollani, S ;
Manzionna, G ;
Porro, GB .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 1999, 11 (01) :27-32
[2]   Biological role of interleukin 1 receptor antagonist isoforms [J].
Arend, WP ;
Guthridge, CJ .
ANNALS OF THE RHEUMATIC DISEASES, 2000, 59 :60-64
[3]   INTERLEUKIN-1 RECEPTOR ANTAGONIST - A NEW MEMBER OF THE INTERLEUKIN-1 FAMILY [J].
AREND, WP .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 88 (05) :1445-1451
[4]   Genetic epidemiology in inflammatory bowel disease [J].
Binder, V .
DIGESTIVE DISEASES, 1998, 16 (06) :351-355
[5]   Evidence for genetic heterogeneity in IBD .1. The interleukin-2 receptor antagonist in the predisposition to suffer from ulcerative colitis [J].
Bioque, G ;
Bouma, G ;
Crusius, JBA ;
Koutroubakis, I ;
Kostense, PJ ;
Meuwissen, SGM ;
Pena, AS .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 1996, 8 (02) :105-110
[6]   INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE POLYMORPHISM AS A DISEASE SEVERITY FACTOR IN SYSTEMIC LUPUS-ERYTHEMATOSUS [J].
BLAKEMORE, AIF ;
TARLOW, JK ;
CORK, MJ ;
GORDON, C ;
EMERY, P ;
DUFF, GW .
ARTHRITIS AND RHEUMATISM, 1994, 37 (09) :1380-1385
[7]   Evidence for genetic heterogeneity in inflammatory bowel disease (IBD); HLA genes in the predisposition to suffer from ulcerative colitis (UC) and Crohn's disease (CD) [J].
Bouma, G ;
Pool, MO ;
Crusius, JBA ;
Schreuder, GMT ;
Hellemans, HPR ;
Meijer, BUGA ;
Kostense, PJ ;
Giphart, MJ ;
Meuwissen, SGM ;
Pena, AS .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 1997, 109 (01) :175-179
[8]  
Calkins BM, 1995, INFLAMM BOWEL DIS, P31
[9]   Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in Northern European Caucasians [J].
Carter, MJ ;
di Giovine, FS ;
Jones, S ;
Mee, J ;
Camp, NJ ;
Lobo, AJ ;
Duff, GW .
GUT, 2001, 48 (04) :461-467
[10]  
CLAY FE, 1994, HUM GENET, V94, P407