rs2066847

Case-control study of 338 Tunisian asthmatic children and 425 healthy controls examining NOD1/NOD2 polymorphisms. The NOD1 rs2075820 (E266K) AA genotype was a significant risk factor for childhood asthma (OR 4.6, p=0.0001), with higher effect in males. NOD1 mRNA and protein expression were significantly elevated in asthma patients (p<0.001).

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 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.

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 case-control association study examined NOD2/CARD15 mutations in IPAA patients with various post-surgical complications. NOD2 mutations were found in 67% of severe pouchitis patients (P<0.001), compared to 5.4% in asymptomatic IPAA patients and 8.5% in healthy controls, suggesting a genetic basis for severe pouchitis due to compromised host immune response to enteric bacteria.

This study tested the association of the CARD8 c.30T>A (p.C10X, rs2043211) variant with Crohn's disease (CD) and ulcerative colitis (UC) in three independent European cohorts (Germany n=497, Hungary n=268, Netherlands n=156 CD patients vs. 832 matched controls). Unlike a previous report suggesting rs2043211 confers CD susceptibility (OR=1.35), no significant association was found across all three cohorts (pooled OR=0.96, p=0.60 for CD), with only a weak trend in Dutch CD patients (p=0.14).

A case-control study of 127 multiple myeloma (MM) cases and 545 controls examined 82 common variants in 45 genes mediating immunity. IL4R rs2107356 (−28120T homozygotes, OR=1.91, 95% CI 1.08-3.38) and FCGR2A rs1801274 (−120G homozygotes, OR=1.95, 95% CI 1.06-3.60) were significantly associated with increased MM risk. A haplotype in the LTA*TNF complex (LTA −82C/−90G*TNF −1036C/−487G/−417G, OR=1.63, 95% CI 1.02-2.61) was also associated with increased MM risk compared to controls.