Age-of-onset-dependent influence of NOD2 gene variants on disease behaviour and treatment in Crohn’s disease

BMC Gastroenterology

Research Article

Georgia Lahr¹  Klaus-Michael Debatin¹  Carsten Posovszky¹  Veronika Pfalzer¹  Benjamin Mayer²  Jan Hendrik Niess³  Jochen Klaus³  Georg BT von Boyen⁴ 

[1] Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstr. 24, 89075, Ulm, Germany;Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany;Internal Medicine, University Medical Center Ulm, Albert Einstein Allee 24, 89081, Ulm, Germany;Medical department of the Academic Clinic Sigmaringen, Hohenzollernstr. 40, 72488, Sigmaringen, Germany;

关键词: Crohn’s disease;    NOD2;    CARD 15;    Osteoporosis;    Pediatric-onset;   

DOI  :  10.1186/1471-230X-13-77

 received in 2012-08-07, accepted in 2013-04-26,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundInfluence 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).Methods85 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).ResultsChronic 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).ConclusionsThese 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.

【 授权许可】

CC BY   
© Posovszky et al.; licensee BioMed Central Ltd. 2013