rs1050152

Two-stage case-control association study in 738 Han Chinese Behcet's disease patients with ocular involvement and 1,873 controls identified three JAK1 SNPs (rs2780815, rs310241, rs3790532) significantly associated with disease susceptibility (Pc=0.030-1.90×10⁻⁴) with population attributable risks of 35.0%, 28.0%, and 27.0% respectively. No significant associations were found for SLC22A4, SLC22A5, or RUNX1 polymorphisms.

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.

A case-control study of 217 Crohn's disease, 252 ulcerative colitis, and 290 control patients in Hungary examining associations with IBD5 locus variants. The IGR2096a_1 T allele (rs12521868) and IGR2198a_1 C allele (rs11739135) showed significantly increased frequencies in Crohn's disease (47.2% and 45.9% vs 38.2% and 37.7% in controls, p<0.05) and were independent risk factors (OR=1.748, 95% CI 1.186-2.574 for T allele; OR=1.646, 95% CI 1.119-2.423 for C allele), while SLC22A4 C1672T and SLC22A5 G-207C variants showed no association.

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 genetic association study of 543 IBD patients (309 CD, 234 UC) and 296 controls found that RUNX3 SNP rs2236851 is associated with ulcerative colitis (OR 1.61, 95% CI 1.11-2.32, P=0.020), with stronger association for pancolitis (OR 1.86). SLC22A4/5 SNPs rs272893 and rs273900 are associated with Crohn's disease (OR 2.16 and 2.40, respectively). An epistatic interaction between RUNX3 and SLC22A4/5 increased UC risk (OR 3.83, P=0.018). RUNX3 mRNA expression is elevated in inflamed colonic mucosa of UC patients.

This case-control study of 316 T1D patients, 599 RA patients, and 540 Spanish controls examined IL4 polymorphisms in the context of the 5q31-33 locus. The IL4 -590C/T polymorphism (rs2243250) showed no individual association with T1D or RA. However, stratified analysis by the OCTN1 L503F variant (rs1050152) revealed a significant association between IL4 and T1D in OCTN1-negative individuals (OR=1.95, 95% CI=1.07-3.55, p=0.02), demonstrating that linkage disequilibrium in this complex region can mask or reveal genetic effects.

This case-control study examined the role of CARD15, TLR4, SLC22A4/5, and DLG5 polymorphisms in 103 pediatric-onset and 696 adult-onset inflammatory bowel disease (IBD) patients compared to 272 healthy controls. CARD15 3020insC homozygosity was significantly more common in pediatric-onset Crohn's disease (CD) versus adult-onset CD (4.2% vs 0.6%, RR 7.1, 95% CI 1.2-42.0, P=0.04). SLC22A4/5 rs3792876 was significantly associated with pediatric-onset CD (6.1% vs 1.1% in adult-onset CD, P=0.02). DLG5 rs2165047 was associated with perianal disease in pediatric CD patients (RR 2.4, 95% CI 1.4-4.0, P=0.003).

This study examined the association of SLC22A4 gene polymorphisms rs3792876 and rs2073838 with bronchodilator response to salbutamol in 180 Egyptian asthmatic patients. The homozygous recessive genotype of rs3792876 was significantly more frequent in non-responders (P = 0.01, OR 1.2-9.5), suggesting this variant may influence drug absorption. The rs2073838 polymorphism showed no significant association with bronchodilator response.

This review examines whether OCTN genes (SLC22A4 and SLC22A5 encoding organic cation transporters) in the 5q31 region are primary susceptibility genes for autoimmune diseases, particularly rheumatoid arthritis and Crohn's disease. Key findings include that OCTN variants (C1672T in SLC22A4 causing Leu503Phe, and -207G>C in SLC22A5 promoter) show association with Crohn's disease in Caucasian populations (frequency ~0.52 in patients vs ~0.42 in controls) and with RA in Japanese populations, but recent evidence suggests these may be in linkage disequilibrium with an unknown causal variant rather than the primary disease genes themselves.