A common haplotype spanning 250 kb in the cytokine gene cluster on chromosome 5q31 has recently been reported to be strongly associated with Crohn disease (CD) in Canadian families. We have replicated this finding by both the transmission-disequilibrium test (TDT) (P=.016) and in a case-control association study (P=.008) in a large European cohort of patients with CD, although the increase in disease risk was small (odds ratio 1.49 for homozygotes, 95% CI 1.11-2.0). No association was detected in families or individuals with ulcerative colitis (UC). Stratification of offspring with CD in the TDT sample by mutation status in the CD susceptibility gene CARD15 showed that the association with the 5q31 risk haplotype was present only in offspring with at least one of the known CARD15 disease susceptibility alleles (P=.044). The 5q31 risk haplotype frequency was 53.1% in unrelated individuals with CD who had one or two CARD15 mutations versus 43.7% in control subjects (P=.0001) but was not significantly elevated in individuals with CD who had no CARD15 mutations (45.4%, P=.41). Kaplan-Meier survival analysis of age at disease onset showed a significantly earlier onset in homozygotes for the 5q31 risk haplotype (P=.0019). These findings suggest that genetic variants at the 5q31 (IBD5) locus may hasten the onset of Crohn disease and cooperate with CARD15 in disease causation.

中文翻译：

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克罗恩病中5q31细胞因子基因座与CARD15基因相互作用的遗传证据。

最近有报道称，在加拿大5q31号染色体的细胞因子基因簇中，一个跨越250 kb的常见单倍型与克罗恩病（CD）密切相关。我们通过传播不平衡测试（TDT）（P = .016）和病例对照关联研究（P = .008）在欧洲大量CD患者中复制了这一发现，尽管疾病增加风险很小（纯合子的比值为1.49，95％CI为1.11-2.0）。在溃疡性结肠炎（UC）的家庭或个人中未发现关联。通过CD易感性基因CARD15中的突变状态，在TDT样品中的CD的后代分层显示，与5q31风险单倍型的关联仅在具有至少一种已知CARD15疾病易感性等位基因的后代中存在（P = .044）。具有一或两个CARD15突变的CD无关个体的5q31风险单倍型频率为53.1％，而对照组为43.7％（P = .0001），但没有CARD15突变的CD个体的5q31风险单倍型频率没有显着升高（45.4％， P = .41）。疾病发作年龄的Kaplan-Meier生存分析显示，对于5q31风险单倍型，纯合子的发作明显更早（P = .0019）。这些发现表明，5q31（IBD5）基因座的遗传变异可能会加速克罗恩病的发作，并在病因上与CARD15协同作用。疾病发作年龄的Kaplan-Meier生存分析显示，对于5q31风险单倍型，纯合子的发作明显更早（P = .0019）。这些发现表明，5q31（IBD5）基因座的遗传变异可能会加速克罗恩病的发作，并在病因上与CARD15协同作用。疾病发作年龄的Kaplan-Meier生存分析显示，对于5q31风险单倍型，纯合子的发作明显更早（P = .0019）。这些发现表明，5q31（IBD5）基因座的遗传变异可能会加速克罗恩病的发作，并在病因上与CARD15协同作用。