rs2241880

A population-based case-control study examined five SNPs in autophagy-related genes (ATG5, ATG10, ATG16L) and melanoma clinical characteristics in 911 patients. ATG16L rs2241880 GG genotype was associated with earlier stage (OR 0.47, P=0.02) and decreased Breslow thickness (P=0.03), while two ATG5 SNPs (rs2245214 CG, OR 1.47, P=0.03; rs510432 CC, OR 1.84, P=0.05) were associated with increased stage. ATG10 rs1864182 CC and ATG5 rs510432 CC were inversely associated with brisk tumor-infiltrating lymphocytes.

A case-control study of 134 rheumatoid arthritis patients and 147 healthy controls found no significant association between the ATG16L1 rs2241880 polymorphism (Thr300Ala, T300A) and RA susceptibility. The rs2241880 polymorphism was in Hardy-Weinberg equilibrium in both groups with no significant differences in genotype or allele frequencies between cases and controls (p=0.772-0.983; OR=0.996).

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 case-control study in a Chinese Han population evaluated eight IBD susceptibility loci previously identified in European GWAS. The study found that NOD2 P268S contributed to Crohn's disease susceptibility (P=0.025), IL23R rs11805303 conferred protective effect against ulcerative colitis (P=0.010), and PTPN2 rs2542151 was associated with increased UC risk (P=0.001). Phenotype-genotype analysis showed P268S was associated with early-onset disease and ileal involvement in CD patients.

JAK2 variant rs10758669 significantly increases susceptibility to Crohn's disease (p=0.026, OR=1.25) and is associated with increased intestinal permeability (p=0.004, OR=2.996), suggesting a barrier dysfunction mechanism in IBD pathogenesis. STAT3 rs744166 also increased CD risk (p=0.04, OR=0.83), while IRGM variants showed no association with disease. The findings highlight JAK2's role in epithelial barrier function independent of NOD2 genotype.

Study of 354 African American Crohn's disease cases and 354 controls examined the contribution of European admixture and major established CD risk genes. Mean European ancestry was similar between cases (20.9%) and controls (20.4%, p=0.58). Significant associations were found with NOD2 carrier status (OR 3.28, p=0.007), ATG16L1 Thr300Ala (p=0.003), IBD5 locus genes SLC22A4 L503F (p=0.05) and SLC22A5 g-207c (p=0.03), and IL23R rs2201841 (p=0.03), but not IRGM variants.

This case-control study in 469 Czech Crohn's disease (CD) patients and 470 controls examined the IBD5 locus, identifying two independent genetic factors: rs6596075 (OR=0.70, protective allele G, p=0.018 in dominant model) and the haplotype tagged by rs2188962 and IGR2063b_1 (OR=1.38 for IGR2063b_1, p=0.00075 in log-additive model). The study demonstrates that these two genetic factors independently contribute to CD susceptibility at the IBD5 locus.

This study examined 40 SNPs (34 CD-associated and 6 UC-associated) in 2374 Canadian IBD patients (1144 CD, 1230 UC/IBDU) and 1057 healthy controls. While most immune-related variants showed similar frequencies between CD and UC, the two diseases diverged significantly in genes related to innate immunity and autophagy (NOD2, ATG16L1, IRGM), which were more prevalent in CD. In patients with colon-only CD, genetic overlap with UC was nearly complete, suggesting a shared genetic basis for colonic disease.

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 GWAS of pediatric IBD patients (n=94) tested associations of known IBD susceptibility loci and novel pharmacogenetic variants with response to anti-TNF α therapy. Non-response occurred in 22 patients (23%). The final predictive model combined UC diagnosis, pANCA positivity, three pharmacogenetic GWAS loci (rs975664 in TACR1 [OR 26.5], rs4855535 in FAM19A4 [OR 10.8], rs6100556 in PHACTR3 [OR 13.8]), and the known susceptibility SNP rs2836878 in BRWD1 (OR 8.0), achieving R²=0.82 and AUC=0.98. The relative risk of non-response increased 15-fold when patients carried ≥3 risk factors.

Meta-analysis of 24 studies (13,022 cases, 17,532 controls) examining the ATG16L1 T300A polymorphism (rs2241880) and Crohn's disease risk. The G allele showed significant association with CD in Caucasians (OR1: 1.87, 95% CI 1.69-2.05 for GG vs AA; OR2: 1.39, 95% CI 1.27-1.51 for GA vs AA) with a co-dominant inheritance model, but no significant association was found in Asians.

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.

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.

This case-control study examined the association of CARD15, IL23R, and ATG16L1 variants with Crohn's disease (CD) susceptibility in a Brazilian population of 187 CD patients and 255 controls. CARD15 variants R702W (OR=3.77) and 3020insC (OR=4.56) and IL23R variants rs1004819 (OR=1.46), rs11209026 (OR=0.36, protective), and rs10889677 (OR=1.38) showed significant associations with CD. However, no significant genotype-phenotype correlations were found for disease location, behavior, or severity in the Brazilian population.

This case-control association study examined the ATG16L1 rs2241880 (Ala197Thr) polymorphism in 2195 Scottish subjects including 361 children with inflammatory bowel disease (IBD), 855 adult IBD patients, and controls. The study confirmed association of the rs2241880G allele with adult-onset Crohn's disease (OR 1.32, P=0.01) but found no association with childhood-onset CD (OR 1.01, P=0.95). Genotype-phenotype analysis revealed the rs2241880G allele was specifically associated with pure ileal disease (OR 1.34, P=0.02), and the difference between childhood and adult disease was attributed to the low frequency of ileal involvement in pediatric cases.

Population-based case-control study (213 CD cases, 315 controls) examining associations between IBD5, IL23R, ATG16L1, and NOD2 genetic variants and Crohn's disease risk. IL23R rs10889677 showed the strongest association with CD (OR=2.47, 95% CI 1.70-3.57), while rs11209026 and rs7517848 were protective (OR=0.44 and OR=0.62 respectively). ATG16L1 Thr300Ala showed strong association (homozygote OR=2.38). Evidence suggested gene-gene interactions between IBD5 and IL23R loci.

This UK case-control replication study of 645 Crohn's disease (CD) and 676 ulcerative colitis (UC) patients confirmed ATG16L1 as a CD susceptibility gene. The nsSNP rs2241880 showed a strong association with CD (P = 2.33 × 10−7, OR 1.45 [1.25–1.67]) with G allele frequencies of 0.52 in controls versus 0.62 in CD cases, but no association was found with UC or any CD subphenotypes. No statistical interactions were detected between ATG16L1 and CARD15, IL23R, or the IBD5 risk haplotype.