title: Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).
abstract: 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(-6) 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(-4) 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.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
authors.forename: Cecília
authors.initials: C
authors.lastname: Durães
authors.forename: José C
authors.initials: JC
authors.lastname: Machado
authors.forename: Francisco
authors.initials: F
authors.lastname: Portela
authors.forename: Susana
authors.initials: S
authors.lastname: Rodrigues
authors.forename: Paula
authors.initials: P
authors.lastname: Lago
authors.forename: Marília
authors.initials: M
authors.lastname: Cravo
authors.forename: Paula
authors.initials: P
authors.lastname: Ministro
authors.forename: Margarida
authors.initials: M
authors.lastname: Marques
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremers
authors.forename: João
authors.initials: J
authors.lastname: Freitas
authors.forename: José
authors.initials: J
authors.lastname: Cotter
authors.forename: Lurdes
authors.initials: L
authors.lastname: Tavares
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Matos
authors.forename: Isabel
authors.initials: I
authors.lastname: Medeiros
authors.forename: Rui
authors.initials: R
authors.lastname: Sousa
authors.forename: Jaime
authors.initials: J
authors.lastname: Ramos
authors.forename: João
authors.initials: J
authors.lastname: Deus
authors.forename: Paulo
authors.initials: P
authors.lastname: Caldeira
authors.forename: Cristina
authors.initials: C
authors.lastname: Chagas
authors.forename: Maria A
authors.initials: MA
authors.lastname: Duarte
authors.forename: Raquel
authors.initials: R
authors.lastname: Gonçalves
authors.forename: Rui
authors.initials: R
authors.lastname: Loureiro
authors.forename: Luísa
authors.initials: L
authors.lastname: Barros
authors.forename: Isabel
authors.initials: I
authors.lastname: Bastos
authors.forename: Eugénia
authors.initials: E
authors.lastname: Cancela
authors.forename: Mário C
authors.initials: MC
authors.lastname: Moraes
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Moreira
authors.forename: Ana I
authors.initials: AI
authors.lastname: Vieira
authors.forename: Fernando
authors.initials: F
authors.lastname: Magro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016207:Cytokines / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D037102:Lectins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C518959:ATG16L1 protein, human; D000893:Anti-Inflammatory Agents; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D016207:Cytokines; D058851:GPI-Linked Proteins; D005819:Genetic Markers; C432397:ITLN1 protein, human; D007166:Immunosuppressive Agents; D037102:Lectins; D019204:GTP-Binding Proteins; C513539:IRGM protein, human