Binion David G, Kugathasan Subra, Dwinell Michael B
Division of Gastroenterology & Hepatology, Froedtert Memorial Lutheran Hospital, Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Am J Gastroenterol. 2006 Jan;101(1):107-9. doi: 10.1111/j.1572-0241.2006.00357.x.
The association of NOD2/CARD15 gene mutations with Crohn's disease (CD) has also provided proof of principle that anatomic location (ileal disease) and stricturing behavior is associated with specific genetic variants. However, the majority of CD patients of Caucasian descent, and essentially all minority CD patients do not possess NOD2/CARD15 mutations. Although these early lessons from NOD2/CARD15 genotype/phenotype correlations are encouraging, much more needs to be done to adequately understand the CD spectrum of subgroups. The study by Brand et al. demonstrates that a chemokine receptor polymorphism (CX3CR1 T280) can also influence disease location and behavior, suggesting yet another genetic variant that can help to subgroup CD patients. Findings similar to the study by Brand and colleagues in this issue of American Journal of Gastroenterology suggest that panels of susceptibility alleles and polymorphisms will ultimately allow an early genetic determination that will correspond with unique clinical patterns of CD: increased expression of the chemokine fractalkine in Crohn's disease and association of the factalkine receptor T280M polymorphism with a fibrostenosing disease phenotype.
NOD2/CARD15基因突变与克罗恩病(CD)的关联也提供了原理证明,即解剖位置(回肠疾病)和狭窄行为与特定的基因变异相关。然而,大多数高加索裔CD患者以及基本上所有少数族裔CD患者都不具有NOD2/CARD15突变。尽管这些来自NOD2/CARD15基因型/表型相关性的早期经验令人鼓舞,但要充分理解CD亚组的范围仍有许多工作要做。布兰德等人的研究表明,一种趋化因子受体多态性(CX3CR1 T280)也会影响疾病位置和行为,这提示了另一种有助于对CD患者进行亚组分类的基因变异。与本期《美国胃肠病学杂志》上布兰德及其同事的研究结果相似的发现表明,一组易感等位基因和多态性最终将实现早期基因判定,这将与CD独特的临床模式相对应:克罗恩病中趋化因子fractalkine的表达增加以及fractalkine受体T280M多态性与纤维狭窄性疾病表型的关联。