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Multidrug resistance 1 gene in inflammatory bowel disease: A meta-analysis

World Journal of Gastroenterology 2006年第23期12卷 3636-3644页

作者： V Annese mr valvano O Palmieri A Latiano F Bossa A Andriulli Unità di Gastroenterologia Ospedale TRCCS "Casa Sollievo detla SofYerenza".San Giovanni Rotondo (Fg)Italy

The MDR1 gene is an attractive candidate gene for the pathogenesis of inflammatory bowel disease （IBD） and perhaps response to therapy, with evidences at both functional and genetic levels. Its product, the P-glycoprotein （P-gp） functions as a transmembrane efflux pump thus influencing disposition and response of many drugs, some of whom （i.e. glucocorticoids） central to IBD therapy. In addition P-gp is highly expressed in many epithelial surfaces, included gastrointestinal tract （G-I） with a putative role in decreasing the absorption of endogenous or exogenous toxins, and perhaps host-bacteria interaction. Many genetic variations of MDR1 gene has been described and in some instances evidences for different P-gp expression as well drugs metabolism have been provided. However data are often conflicting due to genetic heterogeneity and different methodologies employed. Perhaps the greatest piece of evidence of the physiological importance of P-gp in the G-I tract has come from the description of the mdrl knock-out mice model, which develops a spontaneous colitis in a specific pathogen-free environment. Studies investigating MDR1 gene polymorphism and predisposition to IBD have also shown conflicting results, owing to the known difficulties in complex diseases, especially when the supposed genetic contribution is weak. In this study we have undertaken a metaanalysis of the available findings obtained with two SNPs polymorphism （C3435T and G2677T/A） in IBD; a significant association of 3435T allele and 3435TT genotype has been found with UC （OR = 1.17, P = 0.003 and OR = 1.36, P = 0.017, respectively）. In contrast no association with CD and the G2677T/A polymorphism could be demonstrated.

关键词： Inflammatory bowel disease Ulcerative coli-tis Crohn's disease P-glycoprotein Multidrug resistancei gene Meta-analysis

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Role of CARD15,DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases

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World Journal of Gastroenterology 2007年第8期13卷 1221-1229页

作者： S Cucchiara A Latiano O Palmieri AM Staiano R D'Incà G Guariso G Vieni V Rutigliano O Borrelli mr valvano V Annese Clinica Pediatrica Università "La Sapienza" Roma Italy U.O. Gastroenterologia IRCCS "Casa Sollievo della Sofferenza" San Giovanni Rotondo Italy Clinica Pediatrica Università di Napoli Università di Padova Italy Cattedra di Gastroenterologia Università di Padova Italy Clinica Pediatrica Università di Padova Italy Clinica Pediatrica Università di Messina Italy Clinica Pediatrica Università di Bari Italy

AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn's disease CARD15 DLG5, Carnitine/organic cation transporter gene

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