rs2241879

This PhD thesis encompasses multiple studies on pediatric inflammatory bowel disease (IBD): epidemiological analysis shows rising incidence in Scotland (4.45 to 7.82 per 100,000 per year); transmission disequilibrium testing identified rs8126734-A as overtransmitted in IBD and CD (OR 1.48, p=0.047; OR 1.85 for CD, p=0.008); genome-wide association meta-analysis confirmed strong signals in ICOSLG 3'UTR for CD susceptibility; CRP gene variants (rs1417938, rs1130864) showed significant overtransmission (p=0.006, p=0.015); and faecal calprotectin demonstrated superior diagnostic accuracy for PIBD detection (sensitivity 0.93, specificity 0.74).

This study investigated the CXCR3 chemokine axis in inflammatory bowel disease (IBD) across 501 German individuals (336 CD, 165 UC, including 258 children and 243 adults) and 231 controls. CXCR3 axis genes (CXCR3, CXCL9, CXCL10, CXCL11) were significantly overexpressed in inflamed colonic tissue from pediatric CD and UC patients. The CXCL11 rs6817952 A variant showed association with pediatric CD (P=0.04) and UC in all age groups (P=0.009), suggesting a role in IBD pathogenesis.

This case-control association study tested 5 IL23R SNPs and 12 ATG16L1 SNPs in 380 Korean Crohn's disease patients and 380 controls. Two IL23R variants showed significant associations with CD: rs1004819 (aOR=1.822, P=0.009) and rs1495965 (aOR=1.650, P=0.015), with specificity for stricturing and penetrating disease behavior. None of the 12 ATG16L1 SNPs were significantly associated with CD in this Korean population.

This study replicated and meta-analyzed the ATG16L1 Thr300Ala polymorphism (rs2241880) association with inflammatory bowel disease in a Spanish population and 17 additional cohorts. The GG genotype frequency was significantly higher in Crohn's disease patients compared with controls (Spanish cohort: P=0.008, OR=1.28 [1.06-1.54]; meta-analysis: P<10⁻⁴, OR=1.33 [1.28-1.38]), but no significant association was found with ulcerative colitis.