Dataset Information

Systemic complement activation in central serous chorioretinopathy.

ABSTRACT:

Purpose

A clear link between several variants in genes involved in the complement system and chronic central serous chorioretinopathy (CSC) has been described. In age-related macular degeneration, a disease that shows clinical features that overlap with CSC, both genetic risk factors and systemic activation of the complement system have previously been found. In this case-control study, we assessed whether there is evidence of either systemic activation or inhibition of the complement system in patients with chronic CSC.

Methods

A prospective case-control study of 76 typical chronic CSC patients and 29 controls without ophthalmological history was conducted. Complement activity assays (classical, alternative, and mannose-binding lectin pathway), complement factors 3, 4, 4A, 4B, B, D, H, I, and P, activation products C3d, C5a, and sC5b-C9, and the C3d/C3 ratio were analysed in either serum or plasma. A correction for possible effects of gender, age, body mass index, and smoking status was performed.

Results

In this study, none of the tested variables, including regulation and activation products, proved to be significantly different between the groups. Moreover, no associations with either CSC disease activity or possible CSC related steroid use were observed.

Conclusion

Despite the available literature regarding a possible relationship between chronic CSC and variants in genes involved in the complement system, we did not find evidence of an association of chronic CSC with either systemic complement activation or inhibition.

SUBMITTER: van Dijk EHC

PROVIDER: S-EPMC5495432 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Systemic complement activation in central serous chorioretinopathy.

van Dijk Elon H C EHC Tsonaka Roula R Klar-Mohamad Ngaisah N Wouters Diana D de Vries Aiko P J APJ de Jong Eiko K EK van Kooten Cees C Boon Camiel J F CJF

PloS one 20170703 7

<h4>Purpose</h4>A clear link between several variants in genes involved in the complement system and chronic central serous chorioretinopathy (CSC) has been described. In age-related macular degeneration, a disease that shows clinical features that overlap with CSC, both genetic risk factors and systemic activation of the complement system have previously been found. In this case-control study, we assessed whether there is evidence of either systemic activation or inhibition of the complement sy ...[more]

PMID: 28671968

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Project description:ImportanceTo date, several targeted genetic studies on chronic central serous chorioretinopathy (cCSC) have been performed; however, unbiased genome-wide studies into the genetics of cCSC have not been reported. To discover new genetic loci associated with cCSC and to better understand the causative mechanism of this disease, we performed a genome-wide association study (GWAS) on patients with cCSC.ObjectiveTo discover new genetic loci and pathways associated with cCSC and to predict the association of genetic variants with gene expression in patients with cCSC.Design, setting, and participantsThis case-control GWAS was completed in the general community, 3 referral university medical centers, and outpatient care on Europeans individuals with cCSC and population-based control participants. Genotype data was collected from May 2013 to August 2017, and data analysis occurred from August 2017 to November 2017.Main outcomes and measuresAssociations of single-nucleotide polymorphisms, haplotypes, genetic pathways, and predicted gene expression with cCSC.ResultsA total of 521 patients with cCSC (median age, 51 years; interquartile range [IQR], 44-59 years; 420 [80.6%] male) and 3577 European population-based control participants (median age, 52 years; IQR, 37-71 years; 1630 [45.6%] male) were included. One locus on chromosome 1 at the complement factor H (CFH) gene reached genome-wide significance and was associated with an increased risk of cCSC (rs1329428; odds ratio [OR], 1.57 [95% CI, 1.38-1.80]; P = 3.12 × 10-11). The CFH haplotypes H1 and H3 were protective for cCSC (H1: OR, 0.64 [95% CI, 0.53-0.77]; P = 2.18 × 10-6; H3: OR, 0.54 [95% CI, 0.42-0.70]; P = 2.49 × 10-6), whereas haplotypes H2, H4, H5, and the aggregate of rare CFH haplotypes conferred increased risk (H2: OR, 1.57 [95% CI, 1.30-1.89]; P = 2.18 × 10-6; H4: OR, 1.43 [95% CI, 1.13-1.80]; P = 2.49 × 10-3; H5: OR, 1.80 [95% CI, 1.36-2.39]; P = 4.61 × 10-5; rare haplotypes: OR, 1.99 [95% CI, 1.43-2.77]; P = 4.59 × 10-5). Pathway analyses showed involvement of the complement cascade and alternative open reading frame (ARF) pathway in cCSC. Using PrediXcan, we identified changes in predicted expression of complement genes CFH, complement factor H related 1 (CFHR1), complement factor related 4 (CFHR4), and membrane cofactor protein (MCP/CD46). Additionally, the potassium sodium-activated channel subfamily T member 2 (KCNT2) and tumor necrosis factor receptor superfamily member 10a (TNFRSF10A) genes were differentially expressed in patients with cCSC.Conclusions and relevanceIn this GWAS on cCSC, we identified a locus on chromosome 1 at the CFH gene that was significantly associated with cCSC, and we report protective and risk-conferring haplotypes in this gene. Pathway analyses were enriched for complement genes, and gene expression analysis suggests a role for CFH, CFHR1, CFHR4, CD46, KCNT2, and TNFRSF10A in the disease. Taken together, these results underscore the potential importance of the complement pathway in the causative mechanisms of cCSC.

Dataset Information

Systemic complement activation in central serous chorioretinopathy.

Purpose

Methods

Results

Conclusion

Publications

Systemic complement activation in central serous chorioretinopathy.

Similar Datasets

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