CARD15 and HLA DRB1 alleles influence susceptibility and disease localization in Crohn's disease
CARD15 and HLA DRB1 alleles influence susceptibility and disease localization in Crohn's disease
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DOI：
10.1111/j.1572-0241.2004.04038.x
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发表时间：
2004-02-01
影响因子：
9.8
通讯作者：
Siminovitch, K
中科院分区：
文献类型：
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作者：
Newman, B;Silverberg, MS;Siminovitch, K
克罗恩病（CD）是一种与CARD 15和HLA-DRB 1基因的等位基因变体相关的肠道慢性炎症性疾病。我们在加拿大CD队列中调查了这些变体的患病率和影响。方法：对507名无关CD患者进行了三种主要CD相关变体（Arg 702 Trp、Gly 908 Arg和Leu 1007 fsinsC）和十三种HLA-DRB 1等位基因的基因分型。结果：32.5%的CD患者至少存在一种CARD 15变体，而对照组为20%。CARD 15突变的患病率在散发性和家族性以及犹太人和非犹太人CD患者中相似。与非犹太患者相比，犹太患者的Gly 908 Arg变异显著较高，Arg 702 Trp变异显著较低。在非犹太人的家族性病例中检测到HLA-DRB 1 *0103等位基因与CD之间的正相关性（p = 0.0002），与单个或两个CARD 15变异等位基因的1.9倍和19倍相比，HLA-DRB 1 *0103等位基因的存在使CD风险增加6.7倍。我们发现回肠受累与CARD 15变异（OR 1.8; p = 0.02）、HLA-DRB 1 *0701（OR = 1.9; p = 0.006）和DRB 1 *04（OR = 1.7; p 0.02）等位基因显著相关，并证明了CARD 15和HLA-DRB 1基因分型联合预测CD患者回肠疾病的能力。相比之下，HLA-DRB 1 *0103等位基因与诊断年龄晚（p = 0.02）和单纯结肠疾病（p = 0.000013）相关。结论：这些观察结果证实了CARD 15和HLA-DRB 1等位基因对CID易感性和疾病部位的影响，并确定这些变异体的基因分型作为改善CD诊断和风险预测的潜在工具。
OBJECTIVES: Crohn's disease (CD) is a chronic inflammatory disease of the gut associated with allelic variants of CARD15 and HLA-DRB1 genes. We investigated the prevalence and effects of these variants in a Canadian CD cohort.METHODS: 507 unrelated CD patients were genotyped for the three major CD-associated variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) and for thirteen HLA-DRB1 alleles.RESULTS: At least one CARD15 variant was present in 32.5% of the CD patients compared with 20% of controls. The prevalence of CARD15 mutation was similar in both sporadic and familial and Jewish and non-Jewish CD patients. The Gly908Arg variant was significantly higher and the Arg702Trp variant significantly lower in Jewish compared to non-Jewish patients. A positive association between the HLA-DRB1*0103 allele and CD was detected in non-Jewish, familial cases (p = 0.0002), with risk for CD increased by 6.7 fold by the presence of an HLA-DRB1*0103 allele as compared to 1.9 fold and 19 fold by a single or two CARD15 variant alleles, respectively. We show a significant association of ileal involvement with CARD15 variants (OR 1.8; p = 0.02), HLA-DRB1*0701 (OR = 1.9; p = 0.006) and DRB1*04 (OR = 1.7; p 0.02) alleles and demonstrate the capacity of combined CARD15 and HLA-DRB1 genotyping to predict ileal disease in CD patients. By contrast, the HLA-DRB1*0103 allele was associated with later age of diagnosis (p = 0.02) and pure colonic disease (p = 0.000013).CONCLUSIONS: These observations confirm the influence of CARD15 and HLA-DRB1 alleles on both CID susceptibility and site of disease and identify genotyping of these variants as a potential tool for improved diagnosis and risk prediction in CD.