rs3219018

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 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.

This study identifies a promoter polymorphism (rs3219018, -343 G/C) in the FCGR2B gene that is significantly associated with systemic lupus erythematosus (SLE) in European-Americans (OR=11.1, P=0.003). The -343 C/C genotype correlates with decreased transcription of FCGR2B and reduced Fc gamma RIIb receptor expression on activated B cells, suggesting that this genetic variant impairs inhibitory signaling and may contribute to SLE pathogenesis.