Bioinformatics, Scientific Institute IRCCS E. Medea, 23842 Bosisio Parini, LC, Italy.
Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
J Crohns Colitis. 2014 Jun;8(6):489-94. doi: 10.1016/j.crohns.2013.10.014. Epub 2013 Nov 21.
ABO encodes a glycosyltranferase which determines the major human histo-blood group. The FUT2 fucosyltransferase allows expression of ABO antigens on the gastrointestinal mucosa and in bodily secretions (secretor phenotype). A nonsense allele in FUT2 represents a susceptibility variant for Crohn's disease, and both the secretor and ABO blood group status affect the composition of the gut microbiota. Thus, we evaluated if variants in ABO might represent good candidates as Crohn's disease susceptibility loci.
We recruited two case-control cohorts, from Italy (n=1301) and Belgium (n=2331). Subjects were genotyped for one SNP in FUT2 and two variants in ABO.
No effect on Crohn's disease risk was detected for ABO variants, whereas an association was observed between the FUT2 polymorphism and Crohn's disease susceptibility in the Belgian sample, but not in the Italian cohort. The effect of histo-blood groups was evaluated using group O as the reference. Most non-O groups had odds ratios (ORs) higher than 1 in both cohorts, and combined analysis of the two samples indicated a predisposing effect for the A and B groups (OR=1.17, 95% CI: 1.02-1.32 and OR=1.33, 95% CI: 1.09-1.58, respectively). In Crohn's disease patients, the non-O blood group and the non-secretor status were associated with higher risk of developing a stricturing or penetrating disease.
ABO histo-blood group might confer susceptibility to Crohn's disease and modulate disease severity.
ABO 基因编码一种糖基转移酶,决定了人类主要的组织血型。FUT2 岩藻糖基转移酶允许 ABO 抗原在胃肠道黏膜和体液分泌物中表达(分泌表型)。FUT2 中的无义等位基因是克罗恩病的易感变异,分泌表型和 ABO 血型状态均影响肠道微生物群的组成。因此,我们评估了 ABO 中的变异是否可能成为克罗恩病易感性的候选基因。
我们招募了来自意大利(n=1301)和比利时(n=2331)的两个病例对照队列。对受试者进行 FUT2 单核苷酸多态性和 ABO 两个变异的基因分型。
ABO 变异与克罗恩病风险无关联,而 FUT2 多态性与比利时队列的克罗恩病易感性相关,但与意大利队列无关。使用 O 型血作为参考评估了组织血型的作用。在两个队列中,大多数非 O 型组的比值比(OR)均高于 1,两个样本的联合分析表明 A 和 B 组具有易感性(OR=1.17,95%CI:1.02-1.32 和 OR=1.33,95%CI:1.09-1.58)。在克罗恩病患者中,非 O 型血和非分泌表型与发生狭窄或穿透性疾病的风险增加相关。
ABO 组织血型可能与克罗恩病易感性相关,并调节疾病严重程度。