Polymorphisms in interleukin-10 gene according to mutations of NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn's disease

AIM： To examine the contribution of interleukin-10 （IL-10） gene polymorphisms to Crohn＇s disease （CD） phenotype, and the possible genetic epistasis between IL-10 gene polymorphisms and CARD15/NOD2 gene mutations. METHODS： A cohort of 205 Spanish unrelated patients with Crohn＇s disease recruited from a single center was studied. All patients were rigorously phenotyped and followed-up for at least 3 years （mean time, 12.5 years）. The clinical phenotype was established prior to genotyping. RESULTS： The correlation of genotype-Vienna classification groups showed that the Ueocolonic location was significantly associated with the -1082G allele in the NOD2/CARD15 mutation-positive patients （RR = 1.52, 95%CI, 1.21 to 1.91,P= 0.008）. The multivariate analysis demonstrated that the IL-10 G14 microsatellite allele in the NOD2/CARD15 mutation positive patients was associated with two risk factors, history of appendectomy （RR = 2.15, 95%CI = 1.1-4.30, P= 0.001） and smoking habit at diagnosis （RR= 1.29, 95%CI= 1.04-4.3, P= 0.04）. CONCLUSION： In Spanish population from Madrid, in CD patients carrying at least one NOD2/CARD15 mutation, the -1082G allele is assodated with ileocolonic disease and the IL-IOG14 microsatellite allele is associated with previous history of appendectomy and smoking habit at diagnosis. These data provide further molecular evidence for a genetic basis of the clinical heterogeneity of CD.

NOD2/CARD15 gene polymorphism in patients with inflammatory bowel disease: Is Hungary different?

AIM: To analyse the impact of NOD2/CARD15 mutations on the clinical course of Crohn 's disease patients from an eastern European country (Hungary). METHODS: We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 1007finsC) in 148 patients with Crohn's disease, 128 patients with ulcerative colitis and 208 controls recruited from the University of Szeged, Hungary. In patients with Crohn 's disease, the prevalence of NOD2/CARD15 mutations was correlated to the demographical and clinical parameters. RESULTS: In total, 32.4% of Crohn's disease patients carried at least one mutant allele within NOD2/CARD15 compared to 13.2% of patients with ulcerative colitis (P = 0.0002) and to 11.5% of controls (P<O.0001). In Crohn's disease patients, the allele frequencies for Arg702Trp, Gly908Arg and 1007finsC were 7.1%, 3.0% and 10.8% respectively. Interestingly, only the 1007finsC mutation was associated with a distinct clinical phenotype. The patients positive for the 1007finsC mutation suffered more frequently from stenotic disease behaviour (P= 0.008). Furthermore, 51.9% of patients positive for the 1007finsC mutation underwent a surgical resection within the ileum compared to only 17.4% of patients without the 1007finsC mutation (P = 0.001). With respect to the other two mutations (Arg702Trp and Gly908Arg), no associations were found with all investigated clinical parameters. CONCLUSION: NOD2/CARD15 mutations are frequently found in Crohn's disease patients from Hungary. The 1007finsC mutation is associated with stenotic disease behaviour and frequent ileal resections.

Association between NOD2/CARD15 gene polymorphisms and Crohn's disease in Chinese Zhuang patients

AIM: To assess the relationship between the P268S, JW1 and N852S polymorphisms and Crohn&#x02019;s disease (CD) susceptibility in Zhuang patients in Guangxi, China.

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.

NOD2/CARD15 , ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn’s disease

AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn’s disease (CD). METHODS: Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 ; rs2241880 A/G of ATG16L1 , and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (PCR) or by PCR-restriction fragment length polymor-phism analysis. The polymorphisms rs2241880 A/G of the ATG16L1 , and rs11209026 (R381Q) of the IL23R gene in the children’s cohort were genotyped by PCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 5.0 (500K). RESULTS: The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (P = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without co- lonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to con- trols (P = 0.017 and P = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype. CONCLUSION: Polymorphism 3020insC in NOD2/ CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated with susceptibility to CD, but not earlyonset disease.

NOD2/CARD15基因突变与中国人克罗恩病相关性的研究

背景:近年多项研究证明NOD2/CARD15基因序列的单核苷酸多态性(SNP)与西方白种人克罗恩病(CD)明显相关,其中3个SNP(R702W、G908R和3020insC)与CD的相关性尤为显著。目的:探讨NOD2/CARD15基因SNP与中国人CD发病的相关性及其与CD临床特点的关系。方法:选取临床资料完整的CD患者48例、溃疡性结肠炎(UC)患者和健康对照者各50例,提取人血白细胞基因组DNA,经聚合酶链反应(PCR)扩增NOD2基因全部12对外显子,纯化后直接测序,根据结果分析其突变与CD病变特点的关系。结果:CD组、UC组和健康对照组均未检出3个西方人常见的NOD2/CARD15基因多态性位点。CD组的P268S突变率显著高于UC组和健康对照组(P<0.05)。5例P268S突变的CD患者病变均位于回肠(P<0.01),4例发病年龄≤20岁(P<0.01),且均并发肠腔狭窄(P<0.01)。结论:中国人CD患者中存在NOD2/CARD15基因P268S突变,且与患者的发病年龄、病变部位和并发症相关,有必要对其功能作进一步探讨。

P268S突变型NOD2/CARD15真核表达载体的构建及其体外表达

背景:NOD2/CARD15基因序列单核苷酸多态性(SNP)与欧美人群的克罗恩病(CD)明显相关,其中R702W、G908R和3020insC3个SNP位点与CD的相关性尤为显著。而日本、韩国以及我国香港和浙江地区的研究均未发现上述3个SNP的改变,但最近研究发现了可能与中国人CD相关的P268S突变。目的:构建P268S突变型NOD2/CARD15真核表达载体和体外转染体系,为研究突变型NOD2/CARD15的功能提供实验基础。方法:应用定点诱变技术构建P268S突变型NOD2/CARD15真核表达载体,以阳离子脂质体介导体外转染技术瞬时转染人胚肾细胞HEK293T,以蛋白质印迹法和逆转录聚合酶链反应(RT-PCR)检测HEK293T细胞NOD2/CARD15的表达。结果:经克隆、酶切、测序证实获得P268S突变型NOD2/CARD15基因,突变载体转入HEK293T细胞后,NOD2/CARD15有效表达。结论:成功构建了P268S突变型NOD2/CARD15真核表达载体,阳离子脂质体是人胚肾细胞有效的体外转染体系。

NOD2/CARD15基因突变与中国人克罗恩病相关性研究

背景NOD2/CARD15基因是人类克罗恩病(Crohn′sdisease,CD)第一个易感基因,既往研究发现P268S可能与中国人CD发病及临床特征相关。目的本研究旨在证实P268S与中国人CD发病及其临床特征的相关性。方法血样来自临床确诊的50例CD患者,60例溃疡性结肠炎(ulcerativecolitis,UC)患者及100例健康体检者(healthycontrols,HC)。提取人血白细胞基因组DNA,PCR扩增目的片段,PCR-RFLP发现突变位点,DNA测序证实突变位点。结果共有8例CD患者发现有P268S改变,而在UC患者和HC中分别发现2例和3例P268S改变,CD组明显高于UC和HC组(χ2=10.829,P=0.004),而UC组和HC组无明显差异。8例有P268S改变的CD患者临床特征包括病变多位于回肠,发病年龄轻(6例<20岁),常并发肠腔狭窄而需手术治疗,中-重度患者比例高。结论P268S可能是NOD2/CARD15基因中与中国人CD相关的SNP。P268S与CD患者发病年龄、病变部位及并发症及病情严重程度可能相关。

TLR2、TLR4和NOD2/CARD15基因多态性与溃疡性结肠炎相关性的meta分析

背景:近年我国溃疡性结肠炎(UC)的患病率明显增高,Toll样受体2(TLR2)、TLR4和NOD2/CARD15基因多态性与UC的发生、发展可能密切相关。目的:探讨TLR2、TLR4和NOD2/CARD15基因多态性对UC发生的影响。方法:计算机检索PubMed、中国生物医学文献、中国知网、万方数据库、重庆维普等数据库中所有TLR2、TLR4和NOD2/CARD15基因多态性与UC相关性的研究。按照纳入与排除标准筛选文献、评价质量并提取数据,采用RevMan 5.3软件进行meta分析。结果:共纳入15项研究。Meta分析结果显示,TLR2 Arg753Gln基因多态性与UC发生风险无关(P>0.05)。除隐性模型外,TLR4 Asp299Gly基因多态性可显著增加UC的发生风险(P<0.05),TLR4 Thr399Ile基因超显性模型可导致UC风险增加(P<0.05),但显性模型和隐性模型与UC无关(P>0.05)。NOD2/CARD15(Arg702Trp、Gly908Arg、Leu1007fsinsC)基因多态性均与UC无关(P>0.05)。结论:NOD2/CARD15(Arg702Trp、Gly908Arg、Leu1007fsinsC)、TLR2(Arg753Gln)与UC发生风险无关,TLR4(Asp299Gly、Thr399Ile)可增加UC的发生风险。

NOD2/CARD15与炎症性肠病的遗传易感关系的研究进展

炎症性肠病 (IBD)具有遗传易感性 ,主要表现为家族聚集现象、双胞胎显著较高的疾病一致率及不同人群发病率、流行率差异较大。IBD是一个涉及多种因素的复杂性疾病 ,其易感性涉及多个基因位点 ,NOD2 CARD15基因是参与IBD发病的一个重要基因 ,其发现与证实是IBD研究的重大突破 ,为进一步探索IBD的发病机制提供了一条有益途径 ,也为更好的诊断及治疗IBD提供了重要的参考价值。

日本血吸虫卵对TNBS诱导小鼠结肠炎肠黏膜表达NOD2/CARD15的影响

目的研究日本血吸虫卵对2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzesulfonic acid,2,4,6-TNBS)诱导小鼠结肠炎肠黏膜表达NOD2/CARD15的影响。方法实验小鼠(n=50)随机分成3组:正常对照组(n=10)、TNBS+生理盐水组(n=20)和TNBS+日本血吸虫卵组(n=20),后两组用TNBS溶液灌肠(100mg/kg)建立结肠炎模型,TNBS+日本血吸虫卵组在造模前第14天和第3天分别给予腹腔注射冰冻灭活血吸虫卵10000个(1mL冰生理盐水混悬液),TNBS+生理盐水组同时给予相同体积的冰生理盐水腹腔注射,建模后第7天处死存活小鼠,用荧光定量RT-PCR(Real time PCR)法测定结肠组织的NOD2的mRNA基因表达,Western blot方法测定结肠组织NOD2蛋白表达水平。结果TNBS+日本血吸虫卵组死亡率明显下降,结肠肉眼及组织病理炎症程度明显减轻;荧光定量RT-PCR分析显示,TNBS+生理盐水组较正常组结肠黏膜NOD2 mRNA相对表达量显著增加(P<0.01),TNBS+日本血吸虫卵组较TNBS+生理盐水组NOD2 mRNA相对表达量显著下降(P<0.05);Western blot分析显示,TNBS+生理盐水组NOD2的蛋白表达量较正常组增加了近3倍(P<0.01),TNBS+日本血吸虫卵组较TNSB+生理盐水组下降52.8%(P<0.01),差异有显著统计学意义。结论结肠炎时,黏膜NOD2/CARD15表达明显升高,日本血吸虫卵抗原可能通过下调NOD2/CARD15表达改善结肠炎症状态。

NOD2/CARD15与克罗恩病相关性研究进展

克罗恩病(CD)是一种常见的炎症性肠病,是环境因素作用于易感个体产生的肠道慢性非特异性炎症。其发病机制尚未完全明了。NOD2/CARD15是目前确认的第一个与CD相关的基因,通过介导凋亡,调节免疫等多种途径参与CD的发病。本文就NOD2/ CARD15与CD的研究进展作一综述。

NOD2/CARD15基因R702W、G908R及L1007fs多态性与广西壮族人群炎症性肠病的相关性

目的:探讨我国广西壮族人群NOD2/CARD15基因R702W、G908R及L1007fs的遗传多态性与炎症性肠病的相关性.方法:分别收集2007-02/2010-10在广西地区无亲缘关系的壮族(n=70)和汉族(n=76)IBD患者及壮族(n=80)和汉族(n=84)正常对照者的肠黏膜组织.采用酚氯仿法提取各组织样本DNA,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法对NOD2/CARD15基因R702W、G908R及L1007fs进行检测,统计基因型及等位基因频率,分析上述3个多态性位点与广西壮族人群炎症性肠病的相关性.结果:广西壮族和汉族IBD患者与正常对照者均未发现NOD2/CARD15基因R702W、G908R及L1007fs突变型基因型,所有多态性位点上的基因型全部为野生型纯合子,其基因型频率和等位基因频率分布在IBD患者和正常对照者中差异无统计学意义(P>0.05).结论:NOD2/CARD15基因R702W、G908R及L1007fs多态性与广西壮族人群炎症性肠病无明显相关性.

Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

Association between polymorphisms in the Toll-like receptor 4,CD14,and CARD15/NOD2and inflammatory bowel disease in the Greek population

AIM: Crohn's disease(CD)and ulcerative colitis(UC)are multifactorial diseases with a significant genetic background.Apart from CARD15/NOD2 gene, evidence is accumulating that molecules related to the innate immune response such as CD14 or Toll-like receptor 4 (TLR4), are involved in their pathogenesis. In further exploring the genetic background of these diseases, we investigated the variations in the CARD15/NOD2 gene (Arg702Trp,Gly908Arg and Leu1007fsinsC), and polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) as well as in the promoter of the CD14 gene (T/C at position -159) in Greek patients with CD and UC.METHODS: DNA was obtained from 120 patients with CD,85 with UC and 100 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis.RESULTS: The 299Gly allele frequency of the TLR4 gene and the T allele and TT genotype frequendes of the CD14 promoter were significantly higher in CD patients only compared to healthy individuals (P = 0.026＜0.05; P = 0.0048＜0.01 and P= 0.047＜0.05 respectively). Concerning the NOD2/CARD15mutations the overall presence in CD patients was significantly higher than that in UC patients or in controls.Additionally, 51.67% of the CD patients were carriers of a TLR4 and/or CD14 polymorphic allele and at least one variant of the NOD2/CARD15, compared to 27% of the UC patients. It should be pointed out that both frequencies significantly increased as compared with the 10% frequency of multiple carriers found in healthy controls. A possible interaction of the NOD2/CARD15 with TLR4 and especially CD14, increased the risk of developing inflammatory bowel disease (IBD).CONCLUSION: Our results indicate that co-existence of a mutation in either the TLR4 or CD14 gene, and in NOD2/CARD15is associated with an increased susceptibility to developing CD compared to UC, and to developing either CD or UC compared to healthy individuals.

Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn’s disease

AIM： To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn＇s disease （CD）. METHODS： A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn＇s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants （Arg702Trp, Gly908Arg and 2007finsC changes） with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specific regions of these genes. RESULTS： At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profile was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls （9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls）. No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION： The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.

NOD2/CARD15基因突变与克罗恩病的发病及其表型的关系:在以色列阿拉伯裔克罗恩病患者群中的发现

The prevalence of Crohn’ s disease depends on geographic location and racial background. Arg702Trp, Gly908Arg, and Leu1007fsinsC mutations in the NOD2/CARD15 gene are associated with Crohn’ s disease in Caucasians. The mutation rate among Israeli Jewish patients is 27% - 41% . The prevalence of Crohn’ s disease is much lower in the Israeli Arab compared to the Israeli Jewish population. We studied the NOD2/CARD15 mutation rate and disease phenotype (according to the Vienna classification) among the Israeli Arabs and compared them with those in an Israeli Jewish cohort. We recruited 66 Israeli Arab patients and 122 ethnically matched controls. Five patients (8.2% ) and three controls (2.3% ) carried one NOD2/CARD15 mutation. The phenotypic characteristics of the Arab and Jewish patients were very similar. We conclude that NOD2/CARD15 mutations do not contribute to Crohn’ s susceptibility in the Israeli Arab population and suggest that NOD2/CARD15 mutations have an important effect on Crohn’ s prevalence within a specific population but not on the phenotype.

克罗恩病的NOD2/CARD15基因多态性:一项丹麦、葡萄牙患者和对照者中的基因型-表型分析

Background: A North-South gradient in Crohn’s disease (CD) implying a higher incidence in northern Europe compared to southern Europe has been established. Aims: To investigate whether there is a difference between Denmark and Portugal in the frequency of CARD15 mutations in CD patients compared to a healthy background population and to compare genotype-phenotype relations in the two countries. Methods: 58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC. Results: 22%of the Danish patients vs. 9%of Danish controls compared to 21%of the Portuguese patients vs. 16%had at least one mutation. Mutation rates in Danish patients were significantly different (p = 0.02) compared with Danish controls, no difference (p = 0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p = 0.03) using the Mantel-Haenszel test. No difference in evolution of phenotypes and the CARD15 status in CD was found during follow-up between the two matched populations. Ileal disease correlated to high occurrence of CARD15. Conclusion: No North-South gradient regarding occurrence of CARD15 was revealed. Although a trend towards more mutations in the Portuguese controls was seen, a relationship between CD and CARD15 mutations was observed in both countries.

德系犹太裔克罗恩病少儿患者与成年患者的NOD2/CARD15基因突变以及基因型-表现型相关性对比研究

目的:NOD2/CARD15基因位点上的等位基因G908R、R702W和1007fs,与克罗恩病(CD)易感性之间存在显著而独立的相关性。笔者选择犹太裔CD患儿(≤16岁)和成年患者作为研究对象,比较分析两组患者NOD2/CARD15基因位点的基因型以及基因型-表现型相关性。方法:分析67例CD患儿和成年患者基因序列,采用等位基因特异性聚合酶链反应和限制性内切酶酶切反应,检测上述3个等位基因的携带率。同时,检测患者的表现型征象。结果:上述3个NOD2/CARD15 相关性等位基因的携带率,儿童组为51.1%,成年组为37.5%,两组间差异具有统计学显著性,P=0.07。G908R是最常见的等位基因,患儿组携带率为18%,成年患者组为11%,两组间差异具有统计学显著性,P= 0.063。德系犹太裔患儿的G908R等位基因携带率最高,远高于德系成年患者,两组的携带率分别为25%和9%,组间差异具有统计学显著性,P:0.003。患儿多有炎症性肠道疾患家族史,多患炎症性疾病,但与其携带的等位基因改变没有相关性。结论:德系犹太裔少儿幼年期发生的CD,与患儿NOD2/CARD15基因位点上出现G908R等位基因突变型存在密切的关联。

单核苷酸多态性研究表明CARD15/NOD2基因不是银屑病发病的易感基因

Background: A psoriasis susceptibility locus on chromosome 16q was identified recently. This region coincides with a locus predisposing to Crohn’s disease. Patients with Crohn’s disease have a fivefold greater relative risk for devel opment of psoriasis. In Crohn’s disease mutation of the caspase recruitment do main family, member 15 (CARD15) gene (chromosome 16q12.1)-confers susceptibili ty. In light of the overlap in linkage data, and the observation of comorbidity between Crohn’s disease and psoriasis, it is plausible that bot h diseases share a common genetic factor. Objectives: To assess the genetic cont ribution of CARD15 single nucleotide polymorphisms (SNPs) in the pathogenesis of type I psoriasis. Methods: Eight SNPs in CARD15 were genotyped in 148 patients with type I psoriasis and 192 unrelated controls, following a test for populatio n stratification. Genotype and allele frequencies were compared along with estim ated SNP haplotype frequencies. Results: No differences were observed in genotyp e allele or haplotype frequencies between the case and control cohorts. Conclusi ons: The most complete assessment of CARD15 SNPs in type I psoriasis to date rev eals no evidence of association to type I psoriasis.