Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstr, 24, Ulm, 89075, Germany.
BMC Gastroenterol. 2013 May 2;13:77. doi: 10.1186/1471-230X-13-77.
Influence of genetic variants in the NOD2 gene may play a more important role in disease activity, behaviour and treatment of pediatric- than adult-onset Crohn's disease (CD).
85 pediatric- and 117 adult-onset CD patients were tested for the three main NOD2 CD-associated variants (p.R702W, p.G908R and p.10007fs) and clinical data of at least two years of follow-up were compared regarding disease behaviour and activity, response to therapy and bone mineral density (BMD).
Chronic active and moderate to severe course of CD is associated in patients with pediatric-onset (p=0.0001) and NOD2 variant alleles (p=0.0001). In pediatric-onset CD the average PCDAI-Score was significantly higher in patients carrying NOD2 variants (p=0.0008). In addition, underweight during course of the disease (p=0.012) was associated with NOD2 variants. Interestingly, osteoporosis was found more frequently in patients carrying NOD2 variant alleles (p=0.033), especially in pediatric-onset CD patients with homozygous NOD2 variants (p=0.037). Accordingly, low BMD in pediatric-onset CD is associated with a higher PCDAI (p=0.0092), chronic active disease (p=0.0148), underweight at diagnosis (p=0.0271) and during follow-up (p=0.0109). Furthermore, pediatric-onset CD patients with NOD2 variants are more frequently steroid-dependent or refractory (p=0.048) and need long-term immunosuppressive therapy (p=0.0213).
These data suggests that the presence of any of the main NOD2 variants in CD is associated with osteoporosis and an age of onset dependent influence towards underweight, higher disease activity and a more intensive immunosuppressive therapy. This observation supports the idea for an early intensive treatment strategy in children and adolescent CD patients with NOD2 gene variants.
NOD2 基因中的遗传变异可能在儿科发病的克罗恩病（CD）的疾病活动、行为和治疗中发挥更重要的作用，而不是成人发病的 CD。
对 85 例儿科发病和 117 例成人发病的 CD 患者进行了三种主要的 NOD2 CD 相关变异（p.R702W、p.G908R 和 p.10007fs）的检测，并对至少两年的随访临床数据进行了比较，比较内容包括疾病行为和活动、对治疗的反应以及骨矿物质密度（BMD）。
在儿科发病和 NOD2 变异等位基因的 CD 患者中，慢性活动期和中度至重度 CD 病程相关（p=0.0001）。在儿科发病的 CD 中，携带 NOD2 变异的患者的平均 PCDAI-Score 明显更高（p=0.0008）。此外，疾病过程中的体重不足（p=0.012）与 NOD2 变异有关。有趣的是，携带 NOD2 变异等位基因的患者骨质疏松症更为常见（p=0.033），尤其是在携带 NOD2 变异的儿科发病 CD 患者中（p=0.037）。因此，儿科发病 CD 中的低 BMD 与更高的 PCDAI 相关（p=0.0092），与慢性活动期疾病相关（p=0.0148），与诊断时体重不足相关（p=0.0271），与随访期间体重不足相关（p=0.0109）。此外，携带 NOD2 变异的儿科发病 CD 患者更常需要激素依赖或难治（p=0.048），并需要长期免疫抑制治疗（p=0.0213）。
这些数据表明，任何主要的 NOD2 变异在 CD 中都与骨质疏松症以及发病年龄相关的体重不足、更高的疾病活动和更强化的免疫抑制治疗有关。这一观察结果支持对携带 NOD2 基因变异的儿童和青少年 CD 患者进行早期强化治疗策略的想法。
