Prevalence of CARD15/NOD2 mutations in Caucasian healthy people
Prevalence of CARD15/NOD2 mutations in Caucasian healthy people
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DOI：
10.1111/j.1572-0241.2007.01149.x
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发表时间：
2007-06-01
影响因子：
9.8
通讯作者：
Parkes, Miles
中科院分区：
文献类型：
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作者：
Hugot, Jean-Pierre;Zaccaria, Isabelle;Parkes, Miles
背景：白种人的克罗恩病 (CD) 与 CARD15/NOD2 突变有关。 R702W、G908R 和 1007fs 突变占突变染色体的 82%。据估计，纯合子或复合杂合子人群患 CD 的相对风险是一般人群的 10 至 40 倍。这种高风险可能支持这样的观点，即 CARD15/NOD2 变异在个体和人群水平上是强 CD 危险因素。 对象和方法：计算了分布在三大洲的 15 个小组招募的 3,575 名白人健康对照中的 R702W、G908R 和 1007fs 突变的等位基因和基因型频率。进行地理同质性检验，并使用chi(2)检验将观察到的双突变体比例与预期值进行比较。结果：R702W、G908R和1007fs突变的等位基因频率分别为4.3%（3.6-4.9）、1.2%（0.8-1.6）和2.3%（1.8-2.8），地理波动较大。 G908R、1007fs 和野生型等位基因 (P < 0.0001)。在人群水平上，在研究人群中突变频率与疾病发生率之间没有观察到简单的关系。在个体水平上，健康对照中没有发现双剂量突变携带者的显着缺陷，这提供了强有力的证据，表明最危险基因型的外显率较低。结论：总而言之，这些数据证实了 CARD15/NOD2 与其他未知风险辅助因子相互作用。
BACKGROUND: Crohn's disease (CD) has been associated with CARD15/NOD2 mutations in Caucasians. The R702W, G908R, and 1007fs mutations represent 82% of the mutated chromosomes. The relative risk of developing CD in homozygous or compound heterozygous people has been estimated as between 10 and 40 times that of the general population. This high risk may support the opinion that CARD15/NOD2 variants are strong CD risk factors at the individual and population levels.SUBJECTS AND METHODS: The allele and genotype frequencies were calculated for the R702W, G908R, and 1007fs mutations in 3,575 Caucasian healthy controls recruited by 15 groups distributed on three continents. Geographic homogeneity was tested and the observed proportion of double mutants was compared with the expected value using chi(2) tests.RESULTS: The allele frequencies of the R702W, G908R, and 1007fs mutations were 4.3% (3.6-4.9), 1.2% (0.8-1.6), and 2.3% (1.8-2.8), respectively, with large geographic fluctuations of the G908R, 1007fs, and wild-type alleles (P < 0.0001). At the population level, no simple relationship was observed between mutation frequencies and the disease incidences in the studied populations. At the individual level, no significant deficit of double-dose mutation carriers among healthy controls was found, providing strong evidence that the penetrances of the most at-risk genotypes are low.CONCLUSION: Altogether, these data confirm that CARD15/NOD2 acts in interaction with other unknown risk cofactors.