title: IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes.
abstract: Recent genomic research has identified interleukin-23 receptor (IL23R), nucleotide-binding oligomerization domain containing 2 caspase-activation recruitment domain 15 (NOD2/CARD15), autophagy related 16-like 1 (ATG16L1) and paired-like homeobox 2b (PHOX2B) as susceptibility loci for Crohn's Disease (CD). Our aim was to investigate these gene variants in a group of CD patients and to analyse the correlation to sub-phenotypes such as gender, smoking habits, disease behaviour at diagnosis, severity of disease and extra-intestinal manifestations. Nineteen patients with CD and 20 healthy controls were included in the study. The gene variants IL23R rs7517847 and rs11209026, NOD2/CARD15 rs2066845, PHOX2B rs16853571, ATG16L1 rs2241879 and rs2241880 were genotyped by PCR followed by sequencing. The frequency of the G risk allele of IL23R rs7517847 was found to be increased in patients with CD (42%) compared to that in control subjects (20%) [odds ratio (OR), 2.9; 95% confidence interval [CI], 1.06-7.9; P=0.03]. In addition, the homozygous condition GG was also associated with CD (OR, 8.70; 95% CI, 0.9-81.6; P=0.038). The analysis of correlation of genotype to sub-phenotypes showed an association of ATG16L1 rs2241879 with the lack of extra-intestinal manifestations (OR, 0.03; 95% CI, 0.002-0.45; P=0.006), and the patients defined as non-smokers displayed an increased frequency of the risk allele C (P=0.03). The present study confirms the association of the heterozygous and homozygous IL23R rs7517847 variant with CD and suggests an additive effect of smoking to the ATG16L1 rs2241879 C risk allele SNP, in the context of the multifactorial model established for the development of CD and a protective effect of the same allele against extra-intestinal manifestations.
authors.affiliation: Department of Histology, Embryology and Applied Biology, University of Bologna, I-40126 Bologna, Italy. mattia.lauriola2@unibo.it
authors.forename: Mattia
authors.initials: M
authors.lastname: Lauriola
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Ugolini
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivetti
authors.forename: Sara
authors.initials: S
authors.lastname: Nanì
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Rosati
authors.forename: Simone
authors.initials: S
authors.lastname: Zanotti
authors.forename: Isacco
authors.initials: I
authors.lastname: Montroni
authors.forename: Alessio
authors.initials: A
authors.lastname: Manaresi
authors.forename: Davide
authors.initials: D
authors.lastname: Zattoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Belluzzi
authors.forename: Lucia
authors.initials: L
authors.lastname: Castellani
authors.forename: Gabriele
authors.initials: G
authors.lastname: D'Uva
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mattei
authors.forename: Mario
authors.initials: M
authors.lastname: Taffurelli
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Strippoli
authors.forename: Rossella
authors.initials: R
authors.lastname: Solmi
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic; D018123:Receptors, Interleukin / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018398:Homeodomain Proteins; C515500:IL23R protein, human; C109220:NBPhox protein; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin; D014157:Transcription Factors