Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation
Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation
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DOI：
10.1038/gene.2008.96
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发表时间：
2009-04-01
影响因子：
5
通讯作者：
Palou, E.
中科院分区：
文献类型：
--
作者：
Colobran, R.;Casamitjana, N.;Palou, E.
肺移植（LT）已成为晚期肺部疾病患者公认的治疗方法。移植成功的主要限制之一是移植器官的排斥反应，其中趋化因子是关键的介质。在这里，我们测试了CCL4L趋化因子基因拷贝数变异（CNV）与LT患者排斥风险之间的关系（n = 161）。无急性排斥反应的患者的CCL4L拷贝数明显低于急性排斥反应的患者（1.66 vs 1.96, P = 0.014），有一次以上急性排斥反应的患者的CCL4L拷贝数甚至更多（1.66 vs 2.30, P = 0.001）。此外，>= 2个CCL4L拷贝的患者发生急性排斥反应的风险明显高于0-1个CCL4L拷贝的患者（优势比2.65；95%可信区间1.33-5.28;P = 0.0046）。对CCL4L CNV和rs4796195 CCL4L单核苷酸多态性的联合分析表明，CCL4L拷贝数对急性排斥反应的影响主要是由于CCL4L1等位基因变异的拷贝数。这一发现构成了CNV作为同种异体移植排斥反应相关因素的首次报道。基因与免疫（2009）10,254-259；doi: 10.1038 / gene.2008.96;2009年1月15日在线发布
Lung transplantation (LT) has become an accepted therapy for selected patients with advanced lung disease. One of the main limitations to successful LT is rejection of the transplanted organ where chemokines are pivotal mediators. Here, we test the relationship between copy number variation (CNV) in the CCL4L chemokine gene and rejection risk in LT patients (n = 161). Patients with no acute rejection showed a significantly lower mean number of CCL4L copies than patients that showed acute rejection (1.66 vs 1.96, P = 0.014), with an even greater number of gene copies seen in patients with more than one episode of acute rejection (1.66 vs 2.30, P = 0.001). Additionally, patients with >= 2 CCL4L copies had a significantly higher risk of acute rejection compared with patients that had 0-1 CCL4L copies (odds ratio 2.65; 95% confidence interval, 1.33-5.28; P = 0.0046). A combined analysis of CCL4L CNV and the rs4796195 CCL4L single nucleotide polymorphism demonstrated that the effect of CCL4L copy number in acute rejection is mainly because of the number of copies of the CCL4L1 allelic variant. This finding constitutes the first report of CNV as a correlate factor in allograft rejection. Genes and Immunity (2009) 10, 254-259; doi:10.1038/gene.2008.96; published online 15 January 2009