Abstract
Objective: Posner-Schlossman syndrome (PSS), also known as glaucomatocyclitic crisis, is an ocular condition characterized by recurrent attacks of anterior uveitis and raised intraocular pressure. Previous studies by our team and others have identified the genetic association of complement pathway genes with uveitis and glaucoma. This study aimed to investigate the complement genes in PSS patients with the view of elucidating the genetic background of the disease.Methods: A total of 331 subjects (56 PSS patients and 275 controls) were recruited for this study. We selected 27 variants in six complement pathway genes (SERPING1, C2, CFB, CFH, C3, and C5) and detected them using TaqMan single nucleotide polymorphism (SNP) Genotyping Assays. Univariate SNP association analysis, haplotype-based association analysis, gene-gene interaction analysis among complement genes, and genotype-phenotype correlation analysis were performed.Results: Among the 27 variants of six complement pathway genes, the functional variant I62V (rs800292) at the CFH gene was found to be significantly associated with PSS; there was a significant increase in the frequency of A allele and AA homozygosity in PSS patients than in controls (P = 1.79 × 10−4; odds ratio (OR) 2.18, 95% CI: 1.44–3.29; P = 4.65 × 10−4; OR 3.66, 95% CI: 1.70–7.85, respectively). The additive effect of CFH-rs800292 and SERPING1-rs3824988 was identified with an OR of 12.50 (95% CI: 2.16–72.28). Genotype-phenotype analysis indicated that the rs800292 AA genotype was associated with a higher intraocular pressure and higher frequency of recurrence. Unlike a high proportion of human leukocyte antigen (HLA)-B27 positivity in anterior uveitis, only 3 in 56 (5.36%) PSS patients were HLA-B27 positive. In addition, one haplotype block (GC) in the SERPING1 gene showed a nominal association with PSS with an increased risk of 2.04 (P = 0.01; 95% CI: 1.18–3.53), but the P-value could not withstand the Bonferroni correction (Pcorr > 0.05).Conclusion: This study revealed a genetic association of a CFH variant with PSS as well as its clinical parameters, implying that the alternative complement pathway might play an important role in the pathogenesis of PSS. Further studies to enrich the understanding of the genetic background of PSS and the role of the complement system in ocular inflammation are warranted.
Highlights
Posner-Schlossman syndrome (PSS), known as glaucomatocyclitic crisis, is an ocular condition that presents with recurrent anterior uveitis and acutely with markedly elevated intraocular pressure (IOP)
The diagnosis of PSS was based on the following clinical features: repeated episodes of unilateral moderate to high elevation of IOP with blurred vision, mild anterior chamber inflammation and mutton-fat-like keratic precipitates (KPs), open anterior chamber angles under high IOP, and no obvious posterior synechiae of the iris [20]
All the selected single nucleotide polymorphisms (SNPs) conformed to the Hardy-Weinberg equilibrium in the control group
Summary
Posner-Schlossman syndrome (PSS), known as glaucomatocyclitic crisis, is an ocular condition that presents with recurrent anterior uveitis and acutely with markedly elevated intraocular pressure (IOP). It is often classified as secondary inflammatory glaucoma [1, 2]. Multiple genetic loci in human leukocyte antigen (HLA) have been identified to be associated with PSS in Japanese and Chinese populations, such as HLA-Ia, HLA-II, HLA-Bw54, HLA-E, and HLA-G These recent genetic studies have helped shed light on the pathogenesis of the disease, and have suggested that they share common etiologies with other hypertensive uveitic conditions [5,6,7,8]. No specific gene other than HLA has been found to directly cause PSS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
