rs2736340

This study identified and validated three blood-based gene expression biomarkers (POU2AF1, TCL1A, and BLK) that predict bronchiolitis obliterans syndrome (BOS) development in lung transplant recipients more than 6 months before clinical diagnosis. Using microarray profiling in 107 samples (89 for discovery, 25 for validation), the three genes showed areas under the curve of 0.83, 0.77, and 0.78 respectively with p-values < 0.01 in Kaplan-Meier survival analysis, providing a non-invasive blood signature for risk stratification.

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.

Two SNPs in VKORC1 (rs9934438 and rs9923231) were identified as genetic risk factors for systemic lupus erythematosus (SLE) in Asian populations. In discovery cohort (263 SLE cases, 357 controls), both SNPs showed strong associations (OR=2.40-2.45, p=6.1×10^-9 to 2.4×10^-9), which were confirmed in a larger replication cohort (1496 cases, 993 controls) with OR=1.53-1.54 (p=4.3-5.1×10^-6), and remained significant after ancestry adjustment (OR=1.34, p=0.0029-0.0032).

This genome-wide association study (GWAS) of 1,178 dermatomyositis cases and 4,724 controls identified strong associations in the MHC region (P < 5×10⁻⁸ at 80 SNPs) and three novel non-MHC autoimmune-associated variants: PLCL1 (rs6738825, FDR=0.00089), BLK (rs2736340, FDR=0.00031), and CCL21 (rs951005, FDR=0.0076). The findings demonstrate genetic overlap between dermatomyositis and other autoimmune diseases.

This review article by Ota and Kuwana synthesizes genetic studies on systemic sclerosis (SSc), a complex autoimmune disease. Multiple genetic association studies, including GWAS and candidate gene approaches, have identified SSc susceptibility genes primarily involved in innate immunity (IRF4, IRF5, IRF7, IRF8, TNFAIP3), adaptive immune response (TNFSF4, CD247, PTPN22, CSK, STAT4, BLK), IL-12 signaling (IL-12A, IL-12RB1, IL-12RB2, TYK2), apoptosis/autophagy (ATG5, GSDMA, GSDMB, NOTCH4), and vascular homeostasis/fibrosis (PPARG). The review emphasizes that identified risk variants are predominantly located in non-coding regulatory regions and influence gene expression rather than protein structure.

This cross-sectional study of 1906 SLE patients found that European genetic ancestry is protective against lupus nephritis development. A 10% increase in European ancestry was associated with a 15% reduction in renal disease risk (OR 0.85, 95% CI 0.82-0.87, p=1.9×10^-30), independent of socioeconomic status and candidate genes including IRF5 (rs4728142), BLK (rs2736340), STAT4 (rs3024912), and ITGAM (rs9937837).

A doctoral thesis investigating endothelin receptor antagonists (mainly bosentan) for primary prevention of pulmonary hypertension in systemic sclerosis patients. The study reviews genetic variants associated with systemic sclerosis and analyzes clinical outcomes of endothelin receptor antagonist treatment in a cohort of Spanish systemic sclerosis patients, with logistic regression analysis showing a protective effect of bosentan treatment (OR 2.2-4.1) against pulmonary hypertension development.

This review article updates the genetics of systemic sclerosis (SSc), a multifactorial autoimmune disease. Key findings include identification of multiple susceptibility genes through candidate studies (STAT4 rs7574865, PTPN22 rs2476601, CD226 rs763361, TNFAIP3 rs5029939, and others) and genome-wide association studies revealing loci at HLA, STAT4, CD247, TNPO3/IRF5, and novel regions (TNIP1, RHOB). A large GWAS (N=2,296 cases/5,171 controls) identified HLA-DQB1 (rs6457617) as the strongest association and replicated CD247 rs2056626. Gene-gene interaction studies demonstrated additive effects of STAT4, IRF5, and NLRP1 variants on disease susceptibility.

This review updates knowledge on genetic factors in systemic sclerosis (SSc) susceptibility and disease expression. GWAS and candidate gene studies have identified multiple SSc-associated genetic variants primarily located in non-coding regions that influence gene expression through eQTL effects. Major risk genes include those involved in innate immunity (IRF4, IRF5, IRF7, IRF8, TNFAIP3), adaptive immune response (PTPN22, STAT4, TNFSF4, CD247), and cell death pathways (ATG5), while few genes directly involve fibrosis or vascular homeostasis. HLA class II genes associate with SSc-related autoantibodies rather than SSc itself. Multi-omics approaches are needed to characterize the complex molecular architecture and identify biomarkers.

This is a comprehensive review of genetic factors in systemic sclerosis (SSc), a complex autoimmune disease. The review synthesizes findings from candidate gene analysis and genome-wide association studies identifying numerous SNPs and genetic variants associated with SSc susceptibility, primarily in genes involved in innate immunity (IRF4, IRF5, IRF7, IRF8, TNFAIP3), adaptive immunity (TNFSF4, PTPN22, STAT4, BLK, PRDM1), and cell death pathways (ATG5, DNASE1L3, GSDMA/B, NOTCH4). HLA class II genes are associated with SSc-related autoantibodies rather than SSc itself, with DRB1 alleles carrying the FLEDR amino acid sequence critical for anti-topo I antibody responses.

This comprehensive review examines genetic associations in type I interferon-related signaling pathways across multiple autoimmune diseases. The authors review evidence linking dysregulated interferon alpha (IFNα) signaling to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune conditions, identifying multiple susceptibility genes including IFIH1, IRF5, STAT4, TYK2, BLK, BANK1, FCGR2A, and TREX1 with well-replicated associations and functional relevance to IFN pathway dysfunction.

Retrospective case-control study of 222 systemic sclerosis patients with digital ulcers examining whether endothelin receptor antagonist bosentan reduces pulmonary hypertension risk. Bosentan treatment was associated with lower pulmonary hypertension incidence (14% vs 28% in controls, p<0.05) and better echocardiographic parameters in multivariate analysis.