The hypothesis postulating that Mycobacterium avium paratuberculosis(MAP) is the cause of Crohn's disease(CD) has been circulating for many years.Advances in molecular techniques,such as polymerase chain reaction ...The hypothesis postulating that Mycobacterium avium paratuberculosis(MAP) is the cause of Crohn's disease(CD) has been circulating for many years.Advances in molecular techniques,such as polymerase chain reaction and culture methods,have enabled researchers to demonstrate that there is an association between MAP and CD.Recently,genome-wide association studies have identified novel susceptibility genes for CD,which are critical for generation of an adaptive immune response that is protective against intracellular pathogens,including M.tuberculosis infection.However,the role of MAP as a cause of CD suffered a setback with the report that administration of antimycobacterial therapy failed to lead to a sustained response in CD patients.Accordingly,this review sought neither to confirm nor refute this,but instead to survey recent literature on the role of MAP in CD.展开更多
AIM: Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus,IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD)...AIM: Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus,IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD)and ulcerative colitis (UC) patients to determine whether this locus is associated with IBD, and to ascertain the main clinical phenotype influenced by this risk factor. The kind of interaction, either genetic heterogeneity or epistasis, between this IBD5 susceptibility region and the NOD2/CARD15 gene mutations was studied as well.Finally, ve assessed whether this locus can predict response to infliximab therapy.METHODS: A case control study was performed with 274CD and 211 UC patients recruited from a single center and 511 healthy ethnically matched controls. Two polymorphisms were genotyped in the IBD5 locus and three in the CARD15/NOD2 gene.RESULTS: Our results evidence association only with CD especially with the fistulizing phenotype and in the absence of NOD2/CARD15 variants (mutant allele frequency in patients vscontrols: OR = 2.03, 95% CI = 1.35-3.06,P＜0.01). The frequency of the IBD5 homozygous mutant genotype significantly increased in CD patients lacking response to infliximab (RR = 3.88, 95% CI = 1.18-12.0,P＜0.05). UC patients overall do not show association with 5q31 polymorphisms, although a similar trend to the one observed in CD is found within the worse prognosis group.CONCLUSION: The IBD5 variants may enhance an individual carrier's risk for CD, mainly in the absence of the NOD2/CARD15 mutations and in fistulizing patients.The data presented suggest the potential role of the 5q31polymorphisms as markers of response to infiiximab.展开更多
基金Supported by Grant from Fundación de Investigación MédicaMutua Madrileía (Professor M Díaz-Rubio)
文摘The hypothesis postulating that Mycobacterium avium paratuberculosis(MAP) is the cause of Crohn's disease(CD) has been circulating for many years.Advances in molecular techniques,such as polymerase chain reaction and culture methods,have enabled researchers to demonstrate that there is an association between MAP and CD.Recently,genome-wide association studies have identified novel susceptibility genes for CD,which are critical for generation of an adaptive immune response that is protective against intracellular pathogens,including M.tuberculosis infection.However,the role of MAP as a cause of CD suffered a setback with the report that administration of antimycobacterial therapy failed to lead to a sustained response in CD patients.Accordingly,this review sought neither to confirm nor refute this,but instead to survey recent literature on the role of MAP in CD.
基金Supported by grant from MCYT SAP 2003-08522. Elena Urcelay is recipient of a "Ramon y Cajal" contract of the MCYT. Alfonso Martinez is a recipient of a "Post-MIR" contract of the Spanish Health Ministry (01/F011)
文摘AIM: Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus,IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD)and ulcerative colitis (UC) patients to determine whether this locus is associated with IBD, and to ascertain the main clinical phenotype influenced by this risk factor. The kind of interaction, either genetic heterogeneity or epistasis, between this IBD5 susceptibility region and the NOD2/CARD15 gene mutations was studied as well.Finally, ve assessed whether this locus can predict response to infliximab therapy.METHODS: A case control study was performed with 274CD and 211 UC patients recruited from a single center and 511 healthy ethnically matched controls. Two polymorphisms were genotyped in the IBD5 locus and three in the CARD15/NOD2 gene.RESULTS: Our results evidence association only with CD especially with the fistulizing phenotype and in the absence of NOD2/CARD15 variants (mutant allele frequency in patients vscontrols: OR = 2.03, 95% CI = 1.35-3.06,P＜0.01). The frequency of the IBD5 homozygous mutant genotype significantly increased in CD patients lacking response to infliximab (RR = 3.88, 95% CI = 1.18-12.0,P＜0.05). UC patients overall do not show association with 5q31 polymorphisms, although a similar trend to the one observed in CD is found within the worse prognosis group.CONCLUSION: The IBD5 variants may enhance an individual carrier's risk for CD, mainly in the absence of the NOD2/CARD15 mutations and in fistulizing patients.The data presented suggest the potential role of the 5q31polymorphisms as markers of response to infiiximab.
