Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
PLoS One. 2010 Feb 26;5(2):e9453. doi: 10.1371/journal.pone.0009453.
Recent evidence suggests a crucial role of the endocannabinoid system, including the cannabinoid 1 receptor (CNR1), in intestinal inflammation. We therefore investigated the influence of the CNR1 1359 G/A (p.Thr453Thr; rs1049353) single nucleotide polymorphism (SNP) on disease susceptibility and phenotype in patients with ulcerative colitis (UC) and Crohn's disease (CD).
Genomic DNA from 579 phenotypically well-characterized individuals was analyzed for the CNR1 1359 G/A SNP. Amongst these were 166 patients with UC, 216 patients with CD, and 197 healthy controls.
Compared to healthy controls, subjects A/A homozygous for the CNR1 1359 G/A SNP had a reduced risk to develop UC (p = 0.01, OR 0.30, 95% CI 0.12-0.78). The polymorphism did not modulate CD susceptibility, but carriers of the minor A allele had a lower body mass index than G/G wildtype carriers (p = 0.0005). In addition, homozygous carriers of the G allele were more likely to develop CD before 40 years of age (p = 5.9x10(-7)) than carriers of the A allele.
The CNR1 p.Thr453Thr polymorphism appears to modulate UC susceptibility and the CD phenotype. The endocannabinoid system may influence the manifestation of inflammatory bowel diseases, suggesting endocannabinoids as potential target for future therapies.
最近的证据表明，内源性大麻素系统，包括大麻素 1 受体（CNR1），在肠道炎症中起着关键作用。因此，我们研究了 CNR1 1359 G/A（p.Thr453Thr; rs1049353）单核苷酸多态性（SNP）对溃疡性结肠炎（UC）和克罗恩病（CD）患者易感性和表型的影响。
分析了 579 名表型特征良好的个体的基因组 DNA 中 CNR1 1359 G/A SNP。其中包括 166 例 UC 患者、216 例 CD 患者和 197 名健康对照者。
与健康对照组相比，CNR1 1359 G/A SNP 纯合子 A/A 的个体发生 UC 的风险降低（p = 0.01，OR 0.30，95%CI 0.12-0.78）。该多态性不调节 CD 的易感性，但携带 A 等位基因的个体的体重指数低于 G/G 野生型携带者（p = 0.0005）。此外，G 等位基因的纯合子携带者比 A 等位基因携带者更容易在 40 岁之前发生 CD（p = 5.9x10(-7))。
CNR1 p.Thr453Thr 多态性似乎调节 UC 的易感性和 CD 的表型。内源性大麻素系统可能影响炎症性肠病的表现，表明内源性大麻素可能是未来治疗的潜在靶点。
