Institutional members access full text with Ovid®

Share this article on:

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

Durães, Cecília PhD1; Machado, José C. PhD1,2; Portela, Francisco MD3; Rodrigues, Susana MD4; Lago, Paula MD5; Cravo, Marília PhD6; Ministro, Paula MD7; Marques, Margarida MD4; Cremers, Isabelle MD8; Freitas, João MD9; Cotter, José MD10; Tavares, Lurdes MD11; Matos, Leopoldo MD12; Medeiros, Isabel MD13; Sousa, Rui MD14; Ramos, Jaime MD15; Deus, João MD16; Caldeira, Paulo MD17; Chagas, Cristina MD18; Duarte, Maria A. MD19; Gonçalves, Raquel MD20; Loureiro, Rui MD9; Barros, Luísa MD21; Bastos, Isabel MD22; Cancela, Eugénia MD7; Moraes, Mário C. MD23; Moreira, Maria J. MD10; Vieira, Ana I. MD9; Magro, Fernando PhD2,3,24

doi: 10.1002/ibd.23007
Original Basic Science Articles

Background: About 70 loci are associated with susceptibility to Crohn's disease (CD), particularly in pathways of innate immunity, autophagy, and pathogen recognition. Phenotype–genotype associations are inconsistent.

Methods: CD susceptibility polymorphisms ATG16L1 rs2241880, ICAM1 rs5498, IL4 rs2070874, IL17F rs763780, IRGM rs13361189, ITLN1 rs2274910, LRRK2 rs11175593, and TLR4 rs4986790 were genotyped in a Portuguese population (511 CD patients, 626 controls) and assessed for association with CD clinical characteristics.

Results: There is a significant association of CD with the single nucleotide polymorphisms (SNPs) in ATG16L1 (odds ratio [OR] 1.36 [1.15–1.60], P = 2.7 × 10−4 for allele G), IRGM (OR 1.56 [1.21–1.93], P = 3.9 × 10−4 for allele C), and ITLN1 (OR 1.55 [1.28–1.88], P = 4.9 × 10−6 for allele C). These SNPs are associated with ileal location (OR, respectively, 1.49, 1.52, and 1.70), ileocolonic location (OR, respectively, 1.31, 1.57, and 1.68), and involvement of the upper digestive tract (OR, respectively for ATG16L1 and IRGM, 1.96 and 1.95). The risk genotype GG in ATG16L1 is associated with patients who respond to steroids (OR 1.89), respond to immunosuppressants (OR 1.77), and to biologic therapy (OR 1.89). The SNPs in ITLN1 and IRGM are both associated with a positive response to biologic therapy. The risk for ileal, ileocolonic, and upper digestive tract locations increases with the number of risk alleles (OR for three alleles, respectively, 7.10, 3.54, and 12.07); the OR for positive response to biologic therapy is 3.66.

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

Article first published online 9 May 2012

1Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

2Faculty of Medicine of the University of Porto, Porto, Portugal

3Hospital of the University of Coimbra, Coimbra, Portugal

4Hospital of São João, Porto, Portugal

5Hospital of Santo António, Porto, Portugal

6Portuguese Institute of Oncology of Lisbon, Lisbon, Portugal

7Hospital of São Teotónio, Viseu, Portugal

8Hospital of São Bernardo, Setúbal, Portugal

9Hospital of Garcia de Orta, Almada, Portugal

10Hospital Centre of Alto Ave, Guimarães, Portugal

11Hospital of Santa Maria, Lisbon, Portugal

12Hospital of Egas Moniz, Lisbon, Portugal

13Hospital of Évora, Évora, Portugal

14Hospital of Amato Lusitano, Castelo Branco, Portugal

15Hospital of Santo António dos Capuchos, Lisbon, Portugal

16Hospital of Prof. Dr Fernando Fonseca, Amadora, Portugal

17Hospital of Faro, Faro, Portugal

18Hospital of Santa Cruz, Oeiras, Portugal

19Hospital of Divino Espírito Santo, Ponta Delgada, Portugal

20Hospital of São Marcos, Braga, Portugal

21Hospital of Padre Américo, Penafiel, Portugal

22Hospital of Infante D. Pedro, Aveiro, Portugal

23Hospital of Portimão, Portimão, Portugal

24Institute for Molecular and Cell Biology of the Universiy of Porto, Porto, Portugal.

Reprints: Prof. Fernando Magro, Department of Pharmacology and Therapeutics, Faculty of Medicine of the University of Porto, Alameda Prof. Hernani Monteiro 4200-319 Porto, Portugal (e-mail:

Supported by the Portuguese Inflammatory Bowel Disease Group (GEDII 2009 Research Grant); Cecília Durães is supported by the Portuguese Foundation for Science and Technology grant SFRH/BPD/62974/2009. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by the Portuguese Foundation for Science and Technology.

Received March 13, 2012

Accepted April 12, 2012

© Crohn's & Colitis Foundation of America, Inc.
You currently do not have access to this article

To access this article:

Note: If your society membership provides full-access, you may need to login on your society website