Variation at NOD2/CARD15 in familial and sporadic cases of Crohn's disease in the Ashkenazi Jewish population.
Variation at NOD2/CARD15 in familial and sporadic cases of Crohn's disease in the Ashkenazi Jewish population.
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德系犹太人中克罗恩病家族性和散发病例的 NOD2/CARD15 变异。
DOI：
10.1111/j.1572-0241.2002.07105.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Silver,Jack
中科院分区：
文献类型：
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作者：
Zhou,Zhifeng;Lin,Xing-Yu;Akolkar,PradipN;Gulwani-Akolkar,Beena;Levine,Jeremiah;Katz,Seymour;Silver,Jack
目的：最近的报道表明，NOD 2/CARD 15的等位基因变异与克罗恩病（CD）的易感性有关，并且最近定义的三种序列变异中的任何一种在该位点的纯合性或复合杂合性都会大大增加CD的风险。这些序列变化包括两个错义突变，R702 W和G908 R，以及移码插入，1007 insC。本研究的目的是确定这些NOD 2/CARD 15变异的频率在家族性和散发性CD患者的德系犹太人的人口，并确定其对疾病的易感性和发病年龄（AOO）的影响。方法：这三个变种的等位基因和基因型频率确定在481 CD患者的犹太血统和110犹太对照组，169例患者有家族史的CD，312个是“散发”的情况下。结果：家族性病例G908 R变异的频率明显高于散发性病例（0.127 vs 0.059，p= 0.0003），相应地，纯合子和复合杂合子的比例也明显较高（11.8% vs 4.5%，p= 0.0027）。纯合子和复合杂合子的CD的OR为14.6家族性病例和5.1散发病例。对于简单杂合子，CD的风险没有增加。AOO是显着较低的CD患者的纯合子和复合杂合子NOD 2/CARD 15（17.5比22.4年，p= 0.04），但仅为familial cases.CONCLUSIONS：NOD 2/CARD 15有助于更多的CD易感性，在家族性病例比散发病例，和早期AOO。对于仅携带这些NOD 2/CARD 15变体的单个拷贝的个体，CD的风险没有增加，而携带两个拷贝的个体的风险增加了5-15倍。NOD 2/CARD 15突变的突变率估计小于1%。
OBJECTIVE:Recent reports indicate that allelic variants in NOD2/CARD15 are associated with Crohn's disease (CD) susceptibility, and that homozygosity or compound heterozygosity at this locus for any of three recently defined sequence variants confers a greatly increased risk of CD. These sequence changes include two missense mutations, R702W and G908R, and a frameshift insertion, 1007insC. The aim of this study was to determine the frequency of these NOD2/CARD15 variants in familial and sporadic CD patients in the Ashkenazi population and to determine their effects on disease susceptibility and age of disease onset (AOO).METHODS:Allele and genotype frequencies of these three variants were determined in 481 CD patients of Jewish descent and 110 Jewish controls; 169 patients had a family history of CD, and 312 were “sporadic” cases. Variants were detected by polymerase chain reaction using allele-specific primers labeled with fluorescent dye.RESULTS:Familial cases had a significantly higher frequency of the G908R variant than sporadic cases (0.127 vs 0.059, p= 0.0003) and correspondingly, a significantly higher proportion of homozygotes and compound heterozygotes (11.8% vs 4.5%, p= 0.0027). Homozygotes and compound heterozygotes had an OR for CD of 14.6 for familial cases and 5.1 for sporadic cases. There was no increased risk of CD for simple heterozygotes. The AOO was significantly lower for CD patients who were homozygotes and compound heterozygotes for NOD2/CARD15 (17.5 vs 22.4 yr, p= 0.04), but only for familial cases.CONCLUSIONS:NOD2/CARD15 contributes more to CD susceptibility in familial cases than in sporadic cases, and to an earlier AOO. There is no increased risk of CD for individuals carrying only a single copy of these NOD2/CARD15 variants, whereas individuals carrying two copies have a 5–15-fold increased risk. The penetrance of the NOD2/CARD15 mutations was estimated at less than 1%.