rs231775

A two-stage case-control study of 1002 RCC cases and 1022 controls examined associations between lncARSR polymorphisms and renal cell carcinoma (RCC) risk and survival in a Chinese population. rs7859384 GA/GG genotypes were associated with decreased RCC risk across four genetic models (all P < 0.05; OR = 0.77, 95% CI = 0.64-0.94 for stage I/II; OR = 0.79, 95% CI = 0.65-0.95 for clear cell RCC) and higher overall survival (adjusted HR = 0.34, 95% CI = 0.16-0.73, P = 0.005).

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).

A case-control study of 273 DCM patients and 548 controls in the Chinese Han population examined seven genetic variants associated with cardiac neonatal lupus. The study found that the T allele of rs3134942 in NOTCH4 increased DCM risk by 61% (OR=1.61, 95% CI: 1.15-2.27, P=6.57×10⁻³) in additive and dominant models. Additionally, rs2472299 in CYP1A2 was associated with reduced DCM risk in the dominant model (OR=0.72, P=4.24×10⁻²) and correlated with smoking status in patients.

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).

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).

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Population-based case-control study of Connecticut women showing that genetic polymorphisms in IL10RA (rs9610) and TNF (rs1800629) genes modify the association between blood transfusion and non-Hodgkin lymphoma (NHL) risk. IL10RA rs9610 GG genotype carriers with transfusion history had increased NHL risk (OR=1.9, 95% CI: 1.1-3.2), while AG/AA carriers had decreased risk (OR=0.6, 95% CI: 0.4-0.9), with significant gene-transfusion interaction (P=0.003).

A comprehensive review of genetic variants contributing to systemic lupus erythematosus (SLE), covering both polygenic (>100 susceptibility loci) and monogenic (1-10% of cases) contributions identified through NGS techniques. Key susceptibility genes include STAT4, BANK1, TNFAIP3, BLK, IRF5, ETS1, and TNIP1, with early-onset SLE showing greater genetic burden particularly in Black, Asian, and Hispanic ancestries.

This case-control association study evaluated 23 genetic sequence variants in 17 genes across DNA repair, cell cycle, and other pathways in 531 stage I-II radiation-treated head and neck cancer (HNC) patients to identify associations with secondary primary cancers (SPCs). Among the variants tested, the DNMT3B C149T variant (rs2424913) showed a strong significant association with SPC development, with adjusted hazard ratios of 2.23 (95% CI, 1.32-3.78; P = .003) for TT versus CC genotype and 1.49 (95% CI, 1.15-1.95; P = .003) per T allele. A haplotype cluster of 5 DNMT3B variants in strong linkage disequilibrium also showed significant associations (P < .003), suggesting aberrant DNA methylation is an important modulator of field cancerization in HNC.

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 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.

Meta-analysis of 27 case-control studies (9,805 RA patients, 10,691 controls) found that the CTLA-4 A49G polymorphism (rs231775) is significantly associated with increased rheumatoid arthritis risk. The G allele showed elevated risk: GG vs AA OR=1.13 (95% CI 1.03-1.23), GA vs AA OR=1.19 (95% CI 1.07-1.33), and GA+GG vs AA OR=1.18 (95% CI 1.07-1.29). Association was consistent in both Asian and Caucasian populations.

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.

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.

This journal issue contains multiple genetic association studies on rheumatoid arthritis (RA). A key REMARCA study (146 aCCP+ RA patients vs 314 controls) identified polymorphisms in CTLA4 (rs231775 +49A/G), IL10 (rs1800872 -592A/C), and IL6R (rs8192284 +358A/C) associated with high inflammatory disease activity, with CTLA4 and IL10 minor alleles showing increased risk (OR=1.4, p=0.02 and OR=1.9, p<0.0001 respectively) and IL6R minor allele being protective (OR=0.7, p=0.03). A separate study analyzed NOS3, PPARG, PPARGC1A, PPARGC1B and PAI1 polymorphisms in 73 RA patients for cardiovascular risk.

Candidate gene association study of 122 early rheumatoid arthritis (RA) patients and 314 healthy controls found that PTPN22 rs2476601 (OR=1.5, 95% CI 1.0-2.3, p=0.05) and TNFAIP3 rs675520 (OR=1.7) polymorphisms were significantly associated with RA risk. Anti-cyclic citrullinated peptide (ACPA) antibody production was associated with PTPN22, TNFAIP3, CTLA4, and TNF-α polymorphisms in a dose-dependent manner.

Meta-analysis of 27 case-control studies (9,805 RA patients, 10,691 controls) found significant association between CTLA-4 A49G polymorphism (rs231775) and rheumatoid arthritis risk. G allele increased RA susceptibility overall (GA vs AA: OR=1.19) and particularly in Asian populations (GG vs AA: OR=1.34). No publication bias was detected.

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).