IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes

Abstract

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.

ATG16L1 and IL23R Variants and Genetic Susceptibility to Crohnʼs Disease

“…A total of 33 articles, 20,23,24,[27][28][29][30][31]33,35,37,38,[40][41][42]44,47,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] involving 8110 cases and 11,900 controls (Table 2), were included to the meta-analysis regarding the genetic effect of the The overall genetic risk suggested significant protection for the AA genotype (OR G ¼ 0.46; 95% CI, 0.41-0.52). The subgroup analysis on adults 16 20,23,24,[27][28][29][30]33,35,37,38,41,[47][48][49][50]…”

Crohn's disease - genetic factors and progress of the disease

“…A Spanish study found that mutations in the NOD2/ CARD15 are a predictive risk factor for surgical intervention needs due to stricturing affection 25 . Other studies in Central Europe have confirmed the increased probability for surgical intervention 26 , but they found no association of NOD2 mutations with outbreak of the disease at a younger age, isolated ileal disabilities, complicated disease (B2 or B3 under the Montreal classification), as mentioned in some earlier works by other authors 19,22,27 . The presence of two mutations in NOD2 (either homozygous or compound heterozygous) have a higher degree of specificity for the aggressive phenotype 28 .…”

The Role of Autophagy in Crohn’s Disease

“…who initially reported this finding for ATG16L1 in a cohort from the United Kingdom [34], groups in Australia [169] and Portugal [57] have recognised this relationship, with the Portuguese group also showing this association for IRGM. Similarly carriage of the ATG16L1 risk variant has been shown to correlate with a reduction in extra-intestinal manifestations; however the small patient numbers in this report may have been a confounding factor [170]. Another reported positive association was with IRGM variants and the need for ileocolectomy (a surgical procedure to remove the affected distal small bowel and proximal large bowel), however the number of patients in the study again make this difficult to interpret [171].…”