rs800292

The EuroCLOT study identified genetic variants associated with coagulation factors in healthy volunteers and examined their association with ischemic stroke using a three-stage design (2,100 twins in discovery, 4,200 cases in stage 2, and 8,900 cases/55,000 controls in stage 3). The lead ABO locus SNP rs505922 showed significant association with ischemic stroke (OR=1.07, 95% CI=1.03-1.11, p=0.0006), with association specifically in cardioembolic and large-vessel stroke but not small-vessel disease. Two additional ABO SNPs (rs643434 and rs651007) also showed significant association.

Comprehensive review evaluating SNPs as genetic predictors of choroidal neovascularization (CNV) response to photodynamic therapy with verteporfin (PDT-V). The paper examines pharmacogenetic correlations for thrombo-coagulative pathway variants (MTHFR rs1801133, F5 rs6025, F2 rs1799963, F13A1 rs5985), complement/inflammatory variants (CFH, HTRA1, CRP, ARMS2), and VEGFA variants (rs699947, rs2146323), concluding that specific SNPs show clinical plausibility as markers to optimize PDT-V efficacy and guide therapeutic approaches in neovascular macular degeneration.

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.

This is a comprehensive review of the complement factor H (FH) protein family and its role in preventing self-damage from dysregulation of the complement alternative pathway. The paper examines genetic variants in CFH and factor H-related genes (CFHR1-CFHR5) that predispose to age-related macular degeneration, atypical hemolytic uremic syndrome, C3 glomerulopathies, and IgA nephropathy. Key findings include the role of FHR proteins as complement antagonists that compete with FH, and how genetic variations including deletions (ΔCFHR3-CFHR1), hybrid genes, and altered protein expression contribute to disease pathogenesis.

This methods paper describes the development and validation of sequence-specific primer PCR and restriction fragment length polymorphism (RFLP) assays for genotyping three functional polymorphisms in the complement factor H (CFH) gene: rs800292 (V62I), rs1061170 (Y402H), and rs1065489 (E936D). The assays were validated in 271 healthy Hungarian blood donors, with allele frequencies (257G=0.850, 1277T=0.574, 2881G=0.839) consistent with prior reports. The authors identified strong linkage disequilibrium between the Y402H and E936D variants, and found the high-risk haplotype (257G-1277C-2881G) in 16.2% of their young healthy population.

A case-control study of 146 Japanese exudative age-related macular degeneration (ARMD) patients and 105 controls examined complement factor H (CFH) gene polymorphisms. The study identified 61 polymorphisms in the CFH gene but found no association between rs1061170 (Y402H, χ² = 3.19, P = 0.423) or other CFH variants and exudative ARMD in Japanese, despite this SNP showing strong association in Caucasians (χ² = 110.96, P < 10⁻²⁴). The absence of CFH association in Japanese may reflect ethnic differences in ARMD phenotypes and genetic architecture.