Cavanaugh Juleen
Medical Genetics Research Unit, ANU Medical School at the Canberra Hospital, Australian National University, Woden, ACT.
World J Gastroenterol. 2006 Jun 21;12(23):3673-7. doi: 10.3748/wjg.v12.i23.3673.
Investigations into the inheritance of the three risk alleles R702W, G908R and 1007fsInsC in NOD2 associated with susceptibility to Crohn's disease have demonstrated a remarkable amount of heterogeneity across ethnicities and populations, with regional variation across Europe for example, suggesting local founder effects. In non-Caucasian populations Crohn's disease continues to increase in incidence but this increase appears not to be a consequence of variation in NOD2, further advancing the accumulating evidence for other susceptibility loci. Frequencies of the known alleles are compared across populations in health and disease and evidence for additional alleles in NOD2 is reviewed. Based on its position on chromosome 16 coincident with some other autoimmune disease susceptibility localizations, research has targeted NOD2 variation as the potential cause of other autoimmune disorders. While these investigations have mostly returned negative findings, two diseases, Blau Syndrome and Graft versus Host Disease, have been shown to be caused by risk alleles in NOD2. As is frequent in complex disease investigations, some results await validation, but the identification of NOD2 and the differences within and across population raises intriguing questions about the population genetics of the variation at this locus.
对与克罗恩病易感性相关的NOD2基因中三个风险等位基因R702W、G908R和1007fsInsC的遗传研究表明，不同种族和人群之间存在显著的异质性，例如在欧洲存在区域差异，提示存在当地的奠基者效应。在非白种人群中，克罗恩病的发病率持续上升，但这种上升似乎并非NOD2基因变异所致，这进一步支持了其他易感基因座存在的证据。比较了健康人群和患病群体中已知等位基因的频率，并综述了NOD2基因中其他等位基因的证据。基于其在16号染色体上的位置与其他一些自身免疫性疾病易感位点重合，研究将NOD2基因变异作为其他自身免疫性疾病的潜在病因。虽然这些研究大多得到了阴性结果，但已证明两种疾病，即布劳综合征和移植物抗宿主病，是由NOD2基因中的风险等位基因引起的。正如复杂疾病研究中常见的那样，一些结果有待验证，但NOD2基因的鉴定以及群体内部和群体之间的差异，引发了关于该基因座变异群体遗传学的有趣问题。
