rs3087243

This case-control study analyzes 28 SNPs in 26 inflammatory response genes in 343 patients (100 with appendicitis, 243 controls) using TaqMan genotyping. Significant associations were found for IL-13 rs1800925 (OR=6.02, 95% CI 1.52-23.78), IL-17 rs2275913 (OR=2.38, 95% CI 1.24-4.57), and CCL22 rs223888 (OR=0.12, 95% CI 0.02-0.90), suggesting a genetic-driven inflammatory response as a pathogenic mechanism in appendicitis.

This functional study integrates epigenomic datasets (ATAC-seq, Hi-C, ChIP-seq, RNA-seq) from fibroblast-like synoviocytes (FLS) to map the functional relevance of 101 fine-mapped rheumatoid arthritis GWAS associations. FLS regulatory elements account for 24% of RA heritability, and the study assigns putative target genes to RA risk loci, identifying TNFAIP3, IFNAR1, CDK6, RBPJ and others as disease-relevant genes. TNF stimulation reveals dynamic chromatin interactions and differential gene expression at RA-associated regulatory regions.

This study examined two PD-1 gene polymorphisms (rs36084323 and rs11568821) in donors of 1485 HLA-identical sibling hematopoietic stem cell transplants. The rs36084323 GG genotype was associated with increased acute GvHD risk (HR 2.2, P=0.033), while the rs11568821 AA genotype showed much stronger association (HR 4.5, P<0.001). The rs11568821 AA genotype also remained significant for severe (grades III-IV) GvHD (HR 4.15, P<0.001). PD-1 genotype did not significantly affect overall survival, relapse incidence, or chronic GvHD.

This study investigated five CTLA-4 SNPs (rs733618, rs4553808, rs5742909, rs3087243, rs231775) in 86 multiple myeloma patients and 154 controls to evaluate their association with bortezomib treatment outcomes. The rs733618 GG genotype was associated with significantly lower disease-free survival (0% vs 57.4%, P=0.020) and overall survival (46.3% vs 83.3%, P=0.026) compared to GA+AA carriers, with multivariate analysis showing rs733618 GG as a risk factor for overall survival (HR=0.012, 95% CI=0.001-0.199, P=0.002).

This study of 312 donor-recipient pairs undergoing hematopoietic stem cell transplantation found that recipient CT60G>A (rs3087243) [GG] genotype in CTLA-4 is an independent risk factor for acute graft-versus-host disease (aGvHD) with OR 2.63 (95% CI 1.45-4.59, p=0.001), while possessing allele A in both CTLA-4 c.49A>G (rs231775) and CT60G>A polymorphisms decreased aGvHD risk approximately 1.5-fold (RR 0.69, p=0.008).

This candidate gene study of 130 Danish children with type 1 diabetes examined associations between 20 diabetes-related SNPs and diabetic retinopathy progression over 16 years. The CTSH/rs3825932 variant was associated with reduced risk of progression to proliferative diabetic retinopathy (OR=0.20, p=2.4×10⁻³, p_adjust=0.048), while ERBB3/rs2292239 was associated with increased risk of two-step DR progression (OR=2.76, p=7.5×10⁻³, p_adjust=0.15). The CTSH association remained significant after multiple testing correction.

This extended UK genome-wide association study identified a novel rheumatoid arthritis susceptibility locus at 22q12 (rs1043099, P = 6.9 × 10⁻⁹, OR = 0.84) in 3,034 cases and 5,271 controls, and confirmed 16 previously known RA loci, strengthening evidence for genetic contributors to RA in the UK population.

Case-control study of 130 Italian alopecia areata patients and 189 controls examining CTLA4 polymorphisms +49AG (rs231775) and CT60 (rs3087243). CT60 G allele showed significant association with increased disease risk (OR=1.72, p=0.041), particularly in patchy alopecia (OR=2.28, p=0.022). The +49AG polymorphism showed no significant association. Haplotype G(+49AG)-A(CT60) was protective (OR=0.28, p=0.014).

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

This cohort study of 2,324 subjects with inflammatory polyarthritis tested 17 rheumatoid arthritis (RA) susceptibility SNPs for association with all-cause and cardiovascular disease (CVD) mortality. Carriage of the CCL21 risk allele rs2812378 was associated with increased CVD mortality (HR 1.33, 95% CI 1.01-1.75) and all-cause mortality (HR 1.40, 95% CI 1.04-1.87), with the strongest effects observed in anti-CCP antibody-positive patients with both the CCL21 risk alleles and shared epitope (SE) alleles (all-cause HR 3.20, 95% CI 1.52-6.72; CVD HR 3.73, 95% CI 1.30-10.72). SNPs at the TRAF1/C5 locus were not significantly associated with mortality in this study.

This multi-cohort genetic association study of 1,283 RA patients found that the PTPRC/CD45 gene variant rs10919563 (G allele) is associated with favorable response to anti-TNF therapy (OR 0.55, P=0.0001). Of 31 established RA risk alleles tested, only PTPRC reached genome-wide significance for therapy response, with stronger associations in autoantibody-positive patients (OR 0.55, 95% CI 0.39-0.76) compared to seronegative patients.

This case-control association study of juvenile idiopathic arthritis (JIA) in 809 JIA cases and 3,521 controls identified susceptibility loci shared with other autoimmune diseases. Three novel loci were identified: PTPN2 (strongest signals rs7234029, p=7.19×10⁻¹¹, OR=1.59; rs1893217, p=3.48×10⁻⁸, OR=1.52; rs2542151, p=3.05×10⁻⁷, OR=1.45), COG6 (rs7993214, p=3.98×10⁻³, OR=0.79), and ANGPT1 (rs1010824, p=4.93×10⁻³, OR=0.77). Four previously reported JIA loci were confirmed: PTPN22, STAT4, C12orf30, and IL2-IL21. Odds ratios ranged from 1.20 to 1.65 in meta-analysis of initial and independent replication cohorts (n=1,015 cases and 1,568 controls).

This study examined 27 previously identified rheumatoid arthritis (RA) risk alleles in 556 autoantibody-positive African-American RA cases and 791 controls. Twenty-four of 27 SNPs showed consistent odds ratios between African-Americans and Europeans; three SNPs (CCR6 rs3093023, TAGAP rs394581, TNFAIP3 rs6920220) showed opposite directions of effect. A genetic risk score analysis indicated that African-American cases were significantly enriched for European RA risk alleles (p=0.00005), suggesting that RA genetic risk factors are largely shared across ancestry groups.

This case-control study of 591 late-onset Finnish type 1 diabetes patients (ages 15-40) and 1,538 controls identified SNPs at the INS (rs689, OR=0.57, p=2.77×10⁻⁹), PTPN22 (rs2476601, OR=1.50, p=3.98×10⁻⁶), and IFIH1 (rs1990760, OR=0.81, p=0.0028) loci significantly associated with disease. Notably, IL2RA SNPs (rs11594656 and rs41295061) showed no disease association but had independent effects on age at diagnosis (HR=0.83 and 0.74, p=0.015 and 0.006 respectively), making IL2RA a major determinant of disease onset timing.

This case-control study examined 28 SNPs across CD28, CTLA4, and ICOS genes in 763 German melanoma patients and 734 controls to assess association with melanoma susceptibility and prognosis. While two CD28 polymorphisms (rs3181098 and rs3181100) showed differential allele distribution (OR 1.18, P=0.05 and OR 0.83, P=0.02 respectively), after multiple testing correction no convincing associations with melanoma risk or disease prognosis were detected.

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 study investigated the association between three functional CTLA4 polymorphisms (C-318T rs5742909, A49G rs231775, and CT60 rs3087243) and juvenile idiopathic arthritis (JIA) using family-based and case-control analyses in a large cohort (531 JIA families plus 365 independent JIA cases and 551 controls). The authors found no significant associations between any of the CTLA4 variants and JIA overall or most JIA subtypes, and a meta-analysis of published studies also failed to confirm an association between CTLA4 variants and JIA.

In 4,364 type 1 diabetes cases from Great Britain (10.8% positive for thyroid peroxidase autoantibodies [TPOAbs]), the CTLA4 rs3087243 G allele showed a stronger association with disease in TPOAb-positive cases (OR=1.49, 95% CI=1.29-1.72) compared to TPOAb-negative cases (OR=1.16, 95% CI=1.10-1.24, P=0.0004). The TPOAb-positive subgroup showed a marked female bias (1.97:1 female:male ratio) and represents a form of autoimmune polyendocrine syndrome where tolerance to both insulin-producing cells and thyroid tissue is impaired.

This review examines slowly progressive type 1 diabetes mellitus (SPIDDM), also known as latent autoimmune diabetes in adults (LADA), discussing its pathogenesis, diagnostic markers, and genetic associations. Key findings include T-cell-mediated insulitis and pseudoatrophic islets characteristic of type 1 diabetes, absence of amyloid deposition seen in type 2 diabetes, and identification of multiple genetic susceptibility loci including HLA haplotypes, PTPN22 rs2476601, INS rs689, CTLA4, TCF7L2 rs7903146, ZMIZ1 rs12571751, SH2B3 rs7310615, and PFKFB3 rs1983890. GAD autoantibodies and HLA genotypes are important risk factors for beta-cell failure progression.

This case-control study examined CTLA-4 gene polymorphisms (CT60 and +49 A/G) in 114 Egyptian chronic hepatitis C patients receiving interferon-alpha therapy, comparing 54 with thyroid disorders (35 hypothyroidism, 19 Graves' disease) to 60 controls. The AG genotype at +49 was significantly associated with both hypothyroidism (OR: 2.6, 95% CI: 1.1-6.1, P=0.02) and Graves' disease (OR: 2.97, 95% CI: 1.02-8.6, P=0.039), while the CC genotype at CT60 was protective (OR: 2.4 for hypothyroidism, OR: 3.5 for Graves' disease, P<0.05).