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

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World Journal of Gastroenterology 2006年第3期12卷 443-448页

作者： JuanLMendoza ElenaUrcelay RaquelLana AlfonsoMartinez CarlosTaxonera EmilioGdelaConcha manueldíaz-rubio Department of Gastroenterology Hospital Clinico San CarlosUniversidad ComplutenseMadrid Spain Department of ImmunologyHospitai Clínico San CarlosUniversidad Complutense MadridSpain Department of Emergency Hospital Clínico San Carlos.Universidad ComplutenseMadridSpain

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.

关键词： Crohn 's disease NOD2/CARD15 gene Interleukin-10 gene

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Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene

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World Journal of Gastroenterology 2006年第4期12卷 615-620页

作者： ElenaGarcía-Martín JuanLMendoza CarlosTaxonera JoséMLadero manueldíaz-rubio CarmenMartínez JoséAGAgúndez ElenaUrcelay EmilioGdelaConcha Department of Biochemistry & Molecular Biology & Genetics University of ExtremaduraBadajozSpain Service of Gastroenterology Hospital Clinico San CarlosComplutense UniversityMadridSpain Department of Pharmacology University of ExtremaduraBadajozSpain Service of Immunology Hospital Clinico San CarlosComplutense UniversityMadridSpain

AIM： To analyse the role of two common polymorphisms in genes coding for histamine metabolising enzymes as it relates to the risk to develop ulcerative colitis （UC） and the clinical course of these patients. METHODS： A cohort of 229 unrelated patients with UC recruited from a single centre and 261 healthy volunteers were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N-methyltransferase （HNMT） and diamine oxidase （ABP1） enzymes, respectively, by amplification-restriction procedures. All patients were phenotyped and followed up for at least 2 years （mean time 11 years）. RESULTS： There were no significant differences in the distribution of ABP1 alleles between ulcerative colitis patients and healthy individuals [OR （95% CI） for variant alleles = 1.22 （0.91-1.61）]. However, mutated ABP1 alleles were present with higher frequency among the 58 patients that required immunosuppresive drugs [OR （95 % CI） for carriers of mutated alleles 2.41 （1.21-4.83; P=0.006）], with a significant gene-dose effect （P= 0.0038）. In agreement with the predominant role of ABP1 versus HNMT on local histamine metabolism in human bowel, the frequencies for carriers of HNMT genotypes or mutated alleles were similar among patients,regardless clinical evolution, and control individuals. CONCLUSION： The His645Asp polymorphism of the histamine metabolising enzyme ABP1 is related to severity of ulcerative colitis.

关键词： Ulcerative colitis Pharmacogenetics Histamine N-Methyltransferase Diamine Oxidase

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