Phenotype–Genotype Profiles in Crohnʼs Disease Predicted by Genetic Markers in Autophagy-Related Genes (GOIA Study II)

Durães, Cecília; Machado, José Carlos; Portela, Francisco; Rodrigues, Susana; Lago, Paula; Cravo, Marília; Ministro, Paula; Marques, Margarida; Cremers, Isabelle; Freitas, João; Cotter, José; Tavares, L.; Matos, Leopoldo; Medeiros, Isabel; Sousa, Rui; Ramos, Jaime; Deus, João de; Caldeira, Paulo; Chagas, Cristina; Duarte, Maria Antónia; Gonçalves, Raquel; Loureiro, Rui; Barros, Luísa Leite; Bastos, Isabel; Cancela, Eugénia; Moraes, M. C.; Moreira, Maria João; Vieira, Ana Isabel; Magro, Fernando

doi:10.1002/ibd.23007

Cited by 36 publications

(21 citation statements)

References 41 publications

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“…The titles and abstracts of the articles were reviewed and 53 articles were subsequently excluded; the full texts and data integrity for the remaining articles were reviewed and a further 47 studies were excluded. Finally, seven case-control studies were included in the present meta-analysis (17–20,25–27), with publication years that ranged from 2008 to 2013. The selection process of the eligible studies is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

IRGM rs13361189 polymorphism may contribute to susceptibility to Crohn’s disease: A meta-analysis

Lin

et al. 2014

Experimental and Therapeutic Medicine

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The aim of the present meta-analysis was to evaluate the correlation between a common polymorphism, rs13361189 C>T in the immunity-related GTPase M (IRGM) gene, and susceptibility to Crohn’s disease (CD). The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library and CBM databases were investigated from database inception through to October 1, 2013 without the application of any language restrictions. The meta-analysis was performed using STATA 12.0 software and the relative risk (RR) with a 95% confidence interval (CI) was calculated. Seven case-control studies were included with a total of 3,093 CD patients and 3,227 healthy control subjects. The results of the meta-analysis revealed that the IRGM rs13361189 polymorphism correlates with an increased risk of CD (T allele versus C allele: RR=1.25 with 95% CI, 1.04–1.50; P=0.016 and CT + TT versus CC: RR=1.21 with 95% CI, 1.03–1.42; P=0.018). A subgroup analysis conducted using a genotyping method indicated that the IRGM rs13361189 polymorphism was correlated with an increased risk of CD in the TaqMan® (T allele versus C allele: RR=1.32 with 95% CI, 1.01–1.73; P=0.042) and the polymerase chain reaction-restriction fragment length polymorphism subgroups (T allele versus C allele: RR=1.80 with 95% CI, 1.32–2.45; P<0.001 and CT + TT versus CC: RR=1.61 with 95% CI, 1.19–2.18; P=0.018). However, no correlation was observed in the direct sequencing subgroup (P>0.05). Further subgroup analysis by sample size demonstrated significant correlations between the IRGM rs13361189 polymorphism and an increased risk of CD in the large sample-size subgroup (T allele versus C allele: RR=1.46 with 95% CI, 1.26–1.68; P<0.001 and CT + TT versus CC: RR=1.40 with 95% CI, 1.21–1.62; P<0.001). However, no correlation was identified between the IRGM rs13361189 polymorphism and CD risk in the small sample-size subgroup (P>0.05). The present meta-analysis indicated that the IRGM rs13361189 polymorphism may contribute to susceptibility to CD. Thus, IRGM rs13361189 polymorphism may be a potential biomarker for the early diagnosis of CD.

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Section: Resultsmentioning

confidence: 99%

IRGM rs13361189 polymorphism may contribute to susceptibility to Crohn’s disease: A meta-analysis

Lin

et al. 2014

Experimental and Therapeutic Medicine

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“…The titles and abstracts of all articles were reviewed and 53 were excluded; full texts and data integrity were then reviewed and another 51 papers were excluded. A total of 11 case-control studies were included in this meta-analysis (Roberts et al, 2008;Amre et al, 2009;Dema et al, 2009;Latiano et al, 2009;Meggyesi et al, 2010;Wolfkamp et al, 2010;Prager et al, 2012;Wang et al, 2012;Zheng and Pang, 2012;Durães et al, 2013;Moon et al, 2013). Publication years of the eligible studies ranged from 2008-2013.…”

Section: Characteristics Of the Studies Includedmentioning

confidence: 99%

Correlation between IRGM genetic polymorphisms and Crohn’s disease risk: a meta-analysis of case-control studies

Yao

et al. 2014

Genet. Mol. Res.

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ABSTRACT. This meta-analysis was performed to evaluate the relationships between single-nucleotide polymorphisms (SNPs) in the immunity-related GTPase M (IRGM) gene and the risk of Crohn's disease (CD). Eleven case-control studies were included, for a total of 5183 CD patients and 5571 healthy controls. Three common SNPs (rs13361189 C>T, rs10065172 C>T, and rs4958847 A>G) in the IRGM gene were assessed. We found that the IRGM rs13361189 polymorphism was significantly associated with an increased risk of CD [C allele vs T allele: odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.05-1.61, P = 0.017; CC + CT vs TT: OR = 1.32, 95%CI = 1.06-1.64, P = 0.013]. However, we observed no correlation between the rs10065172 and rs4958847 polymorphisms in the IRGM gene with susceptibility to CD (all P > 0.05). Subgroup analysis by ethnicity revealed significant associations between IRGM genetic polymorphisms and an increased risk of CD among Caucasian populations (C allele vs T allele: OR = 1.22, 95%CI = 1.07-1.40, P = 0.004; CC + CT vs TT: OR = 1.22, 95%CI = 1.05-1.41, P = 0.009), but not among Asian populations (all P > 0.05). Meta-regression analysis also confirmed that ethnic differences may be an important source of heterogeneity (P = 0.003). Our meta-analysis results indicate that the IRGM rs13361189 polymorphism contributes to the susceptibility to CD. Thus, the IRGM rs13361189 polymorphism is promising as a biomarker for early diagnosis of CD. However, the IRGM rs10065172 and rs4958847 polymorphisms may not be the major determinants of CD risk.

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“…Autophagy-related genes (ATG16L1, IRGM) and genes encoding pattern-recognition receptors (e.g. NOD2), were identified as CD susceptibility loci/genes by genomewide association studies [15][16][17], suggesting an important contribution of innate immunity in CD immunopathology. Although it has been known that normal intestinal macrophages show low proinflammatory activity, it has been shown that in intestinal diseases, particularly in CD, their profile differs considerably [13].…”

Section: Introductionmentioning

confidence: 99%

Infliximab therapy increases the frequency of circulating CD16+ monocytes and modifies macrophage cytokine response to bacterial infection

Nazareth

Magro

Silva

et al. 2014

Clinical and Experimental Immunology

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SummaryCrohn's disease (CD) has been correlated with altered macrophage response to microorganisms. Considering the efficacy of infliximab treatment on CD remission, we investigated infliximab effects on circulating monocyte subsets and on macrophage cytokine response to bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, treated or not with infliximab. Macrophages were infected with Escherichia coli, Enterococcus faecalis, Mycobacterium avium subsp. paratuberculosis (MAP) or M. avium subsp avium, and cytokine levels [tumour necrosis factor (TNF) and interleukin (IL)-10] were evaluated at different time-points. To evaluate infliximab-dependent effects on monocyte subsets, we studied CD14 and CD16 expression by peripheral blood monocytes before and after different infliximab administrations. We also investigated TNF secretion by macrophages obtained from CD16 + and CD16 − monocytes and the frequency of TNF + cells among CD16 + and CD16 − monocyte-derived macrophages from CD patients. Infliximab treatment resulted in elevated TNF and IL-10 macrophage response to bacteria. An infliximab-dependent increase in the frequency of circulating CD16 + monocytes (particularly the CD14 ++ CD16 + subset) was also observed (before infliximab: 4·65 ± 0·58%; after three administrations: 10·68 ± 2·23%). In response to MAP infection, macrophages obtained from CD16 + monocytes were higher TNF producers and CD16 + macrophages from infliximab-treated CD patients showed increased frequency of TNF + cells. In conclusion, infliximab treatment increased the TNF production of CD macrophages in response to bacteria, which seemed to depend upon enrichment of CD16 + circulating monocytes, particularly of the CD14 ++ CD16 + subset. Infliximab treatment of CD patients also resulted in increased macrophage IL-10 production in response to bacteria, suggesting an infliximab-induced shift to M2 macrophages.

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Phenotype–Genotype Profiles in Crohnʼs Disease Predicted by Genetic Markers in Autophagy-Related Genes (GOIA Study II)

Abstract: A multilocus approach using autophagy-related genes provides insight into CD phenotype-genotype associations and genetic markers for predicting therapeutic responses.

Cited by 36 publications

References 41 publications

IRGM rs13361189 polymorphism may contribute to susceptibility to Crohn’s disease: A meta-analysis

IRGM rs13361189 polymorphism may contribute to susceptibility to Crohn’s disease: A meta-analysis

Correlation between IRGM genetic polymorphisms and Crohn’s disease risk: a meta-analysis of case-control studies

Infliximab therapy increases the frequency of circulating CD16+ monocytes and modifies macrophage cytokine response to bacterial infection

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