rs396991

A retrospective cohort study of 282 patients with severe uncontrolled asthma treated with omalizumab, mepolizumab, or benralizumab for 12 months evaluated genetic variants in 11 genes (IL1RL1, IL5, GATA2, IKZF2, RAD50, C3, FCER1A, FCER1B, FCGR2A, FCGR2B, FCGR3A) as predictors of response. Key findings: FCGR2B rs3219018-C, GATA2 rs4857855-T, and FCGR2A rs1801274-AG associated with improved lung function in omalizumab (p=0.052, 0.052, 0.012); IL1RL1 rs17026974-AG/GG associated with reduced exacerbations in omalizumab (p=0.040, 0.041); FCER1B rs569108-AA and FCGR2A rs1801274-GG associated with corticosteroid reduction in benralizumab; FCER1A rs2427837-A associated with improved lung function in mepolizumab (p=0.023).

This retrospective analysis of the NSABP B-31 randomized trial (1,251 patients with node-positive HER2-positive breast cancer) examined the association between FCGR2A and FCGR3A polymorphisms and trastuzumab benefit. The FCGR3A-158 V/F polymorphism showed significant interaction with trastuzumab treatment: patients with V/V or V/F genotypes had substantially greater benefit from trastuzumab (HR 0.31, 95% CI 0.22-0.43, P<.001 for interaction), while F/F homozygotes showed minimal benefit (HR 0.71, 95% CI 0.51-1.01). FCGR2A-131 polymorphism showed a dose-response relationship but the interaction was not statistically significant.

This study investigates FCGR3A variants (specifically positions 66 and 176) and their functional effects on human IgG binding in relation to systemic lupus erythematosus (SLE) and lupus nephritis. Using flow cytometry-based binding assays on transfected cells and genotyping of 1728 SLE patients and 2404 healthy controls, the authors found that the low binding haplotypes (66R/H/L and 176F combination) confer enhanced risk for lupus nephritis in African Americans (p=0.0609, OR=1.25, 95% CI 0.99-1.57), though FCGR3A copy number variations were not associated with SLE or nephritis.

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.

This study examined hemolytic anemia in 628 SLE patients from the LUMINA multiethnic cohort, analyzing associations with FCGR and Fas/FasL polymorphisms and clinical outcomes. Key findings: FCGR2B-I131T, FasL-205, and FasL-844 polymorphisms showed association with hemolytic anemia; independent risk factors for hemolytic anemia included African American ethnicity (OR 4.21), thrombocytopenia (OR 2.38), and azathioprine use (OR 2.25). Hemolytic anemia was associated with damage accrual but not mortality.