Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Inflamm Bowel Dis. 2012 Dec;18(12):2357-9. doi: 10.1002/ibd.22944. Epub 2012 Mar 22.
Crohn's disease (CD) is highly heritable. NOD2 has emerged as the main susceptibility gene among individuals of European ancestry; however, NOD2 does not appear to contribute to CD susceptibility among many non-European populations. Today's African American (AA) population represents an admixture of West African (80%) and European (20%) ancestry. Since genotype-based tools are becoming increasingly available for CD, it is important that we validate the risk variants in different populations, such as admixed AAs.
We analyzed the NOD2 variants among admixed AAs (n = 321, 240 with CD and 111 healthy controls [HCs]) and nonadmixed West Africans (n = 40) by genotyping four known disease-causing NOD variants. We extracted the publicly available 1000 Genomes data on NOD2 variants from 500 subjects of West African origin. Association with disease was evaluated by logistic regression.
An association with CD was found for the classical single nucleotide polymorphism (SNP) 1007fs (2.6% CD, 0% HC, P = 0.012); there was no association when the genotypic and allelic frequencies of the risk alleles were compared for SNPs R702W and G908R. No known NOD2 risk alleles were seen in either the West African cohort or in subjects of African ancestry from the 1000 Genomes project.
The NOD2 gene is a risk for CD in AAs, although the allele frequencies and the attributable risk are much lower compared with Caucasians. The risk alleles are not seen in the West African population, suggesting that the risk for CD contributed by NOD2 among AAs is due exclusively to recent European admixture.
克罗恩病（CD）具有高度遗传性。NOD2 已成为欧洲血统个体的主要易感基因；然而，NOD2 似乎并未导致许多非欧洲人群的 CD 易感性。如今的非裔美国人（AA）群体是西非（80%）和欧洲（20%）血统的混合体。由于基于基因型的工具越来越多地应用于 CD，因此在不同人群中验证风险变异，例如混合 AA 人群，非常重要。
我们通过对四个已知的致病 NOD 变异进行基因分型，分析了混合 AA（n = 321，240 例 CD 和 111 例健康对照 [HC]）和非混合西非人（n = 40）中的 NOD2 变异。我们从西非起源的 500 名受试者中提取了可公开获得的 1000 基因组数据中关于 NOD2 变异的数据。通过逻辑回归评估与疾病的关联。
发现经典单核苷酸多态性（SNP）1007fs 与 CD 相关（2.6% CD，0% HC，P = 0.012）；当比较 SNPs R702W 和 G908R 的风险等位基因的基因型和等位基因频率时，没有关联。在西非队列或 1000 基因组项目中的非洲裔受试者中均未发现已知的 NOD2 风险等位基因。
NOD2 基因是 AA 中 CD 的风险因素，尽管与白种人相比，等位基因频率和归因风险要低得多。在西非人群中未发现风险等位基因，这表明 NOD2 导致 AA 中 CD 的风险仅归因于最近的欧洲混合。
