rs1801274

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).

A genome-wide association study (GWAS) and targeted resequencing in 364 heparin-induced thrombocytopenia (HIT) cases and controls identified a significant locus on chromosome 5 near rs1433265 (P=2.7×10⁻⁸, OR=2.77). Fine mapping revealed a risk-conferring haplotype (P=4.9×10⁻⁶, OR=2.41), while rare variant analysis identified DDR1 and MCTP2 as candidate genes, and discovered missense variants in ADAMTS16 and ICE1 that may contribute to HIT susceptibility.

This pilot screening study evaluated 32 SNPs in viral immune response genes for association with hospitalized seasonal influenza in adults of European ancestry using a discovery group (26 cases, 993 controls) and two validation groups (84 cases, 4,076 controls; 128 cases, 9,187 controls). The study failed to replicate the previously reported association between IFITM3 rs12252 and hospitalized influenza (P > 0.05), and a preliminary finding of association with SLFN13 rs8072510 (P = 0.0099 in discovery group) was not confirmed in validation groups.

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.

Association study of 6 GWAS-identified susceptibility SNPs with Kawasaki disease in 358 Han Chinese patients and 815 controls. Risk alleles of rs1801274 (FCGR2A, OR=1.33) and rs2254546 (BLK, OR=1.44) showed significant associations. Meta-analyses confirmed significant effects for rs113420705 (CASP3, OR=1.40), rs2857151 (HLA, OR=1.41), and rs4813003 (CD40, OR=1.37). A 3-locus combination (rs113420705 + rs2857151 + rs4813003) showed the strongest association (OR=2.15, P=0.0003), suggesting additive genetic effects on disease susceptibility and coronary artery lesion formation.

Candidate gene association study of 67 genetic variants in 27 inflammation and DNA repair genes with hepatitis A virus (HAV) infection susceptibility in 6,779 NHANES III participants (2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, 2,065 Mexican Americans). Among Mexican Americans, ABCB1 rs1045642 T allele was associated with lower HAV seropositivity risk (OR=0.79, p<0.001), while TGFB1 rs1800469 and XRCC1 rs1799782 T alleles were associated with increased risk (OR=1.38 and 1.57, respectively). CAT rs769214 and CYP2E1 rs2031920 showed marginal associations with decreased and increased HAV risk, respectively.

Genome-wide association study of 116 children with cardiac neonatal lupus (116 cases, 3,351 controls) identified 17 significant SNPs in the HLA region at 6p21, with the strongest association at rs3099844 (OR 3.34, P=4.52×10⁻¹⁰) near the MICB gene. Non-HLA associations were found at rs743446 (21q22, OR 2.40, P=5.45×10⁻⁶), rs2403106 (12q21, OR 2.48, P=2.62×10⁻⁶), rs1391511 (10p15, OR 1.84, P=6.6×10⁻⁶), and rs1890645 (1q31, OR 2.98, P=3.52×10⁻⁶). Results suggest genetic polymorphisms in inflammatory and apoptotic pathways contribute to cardiac injury in fetuses exposed to maternal anti-Ro/SSA antibodies.

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.

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.