Silverberg Mark S, Mirea Lucia, Bull Shelley B, Murphy Janet E, Steinhart A Hillary, Greenberg Gordon R, McLeod Robin S, Cohen Zane, Wade Judith A, Siminovitch Katherine A
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Inflamm Bowel Dis. 2003 Jan;9(1):1-9. doi: 10.1097/00054725-200301000-00001.
The aim of this study was to identify major histocompatibility complex alleles associated with the development and clinical features of inflammatory bowel disease (IBD). Genotyping at the human leukocyte antigen (HLA) DRB1 and DQB1 loci was performed on individuals from 118 Caucasian IBD sibling pair families and on 216 healthy controls. Both population- and family-based association tests were used to analyze data obtained on the entire study population and on clinical subgroups stratified by diagnosis, ethnicity, and disease distribution. HLA DRB10103 was significantly associated with IBD (OR = 6.0, p = 0.0001) in a case-control analysis of non-Jewish IBD-affected individuals. This association was apparent among both Crohn's disease (OR = 5.23, p = 0.0007) and ulcerative colitis (OR = 7.9, p = 0.0001) patients and was confirmed in the non-Jewish IBD population by results of family-based association analysis using the transmission disequilibrium test. HLA DQB10501 was also associated with IBD (OR = 1.64, p = 0.02) in the non-Jewish population. but statistically significant association of this allele with disease was not detected for Crohn's disease and ulcerative colitis separately. No significant associations were identified among the Jewish patients. In the non-Jewish IBD families, IBD was as strongly associated with the DRB10103 DQB10501 haplotype as with the DRB10103 allele alone. The carrier frequency of the DRB10103 allele was found to be 10-fold higher in Crohn's disease patients with pure colonic involvement than in healthy controls (38.5% vs. 3.2%; p = 0.0002). These data demonstrate the association of the HLA DRB10103 allele with both Crohn's disease and ulcerative colitis and with large intestine-restricted disease in non-Jewish IBD patients and therefore identify HLA DRB10103 as a potentially important contributor to disease susceptibility and to expression of colonic involvement in IBD.
本研究的目的是确定与炎症性肠病（IBD）的发生发展及临床特征相关的主要组织相容性复合体等位基因。对118个白种人IBD同胞对家庭的个体以及216名健康对照者进行了人类白细胞抗原（HLA）DRB1和DQB1位点的基因分型。采用基于人群和基于家系的关联检验来分析在整个研究人群以及按诊断、种族和疾病分布分层的临床亚组中获得的数据。在对非犹太裔IBD患者的病例对照分析中，HLA DRB10103与IBD显著相关（OR = 6.0，p = 0.0001）。这种关联在克罗恩病（OR = 5.23，p = 0.0007）和溃疡性结肠炎（OR = 7.9，p = 0.0001）患者中均很明显，并通过使用传递不平衡检验的基于家系的关联分析结果在非犹太裔IBD人群中得到证实。HLA DQB10501在非犹太人群中也与IBD相关（OR = 1.64，p = 0.02），但未分别检测到该等位基因与克罗恩病和溃疡性结肠炎的疾病关联具有统计学意义。在犹太患者中未发现显著关联。在非犹太裔IBD家庭中，IBD与DRB10103 DQB10501单倍型的关联程度与仅与DRB10103等位基因的关联程度相同。发现纯结肠受累的克罗恩病患者中DRB10103等位基因的携带频率比健康对照者高10倍（38.5%对3.2%；p = 0.0002）。这些数据证明了HLA DRB10103等位基因与非犹太裔IBD患者的克罗恩病和溃疡性结肠炎以及大肠局限性疾病均相关，因此确定HLA DRB10103是疾病易感性以及IBD中结肠受累表现的一个潜在重要因素。
