Effect of rare coding variants in the CFI gene on Factor I expression levels.

Human Molecular Genetics
Sarah de JongAnneke I den Hollander

Abstract

Factor I (FI) is one of the main inhibitors of complement activity, and numerous rare coding variants have been reported in patients with age-related macular degeneration, atypical hemolytic uremic syndrome and C3 glomerulopathy. Since many of these variants are of unknown clinical significance, this study aimed to determine the effect of rare coding variants in the complement factor I (CFI) gene on FI expression. We measured FI levels in plasma samples of carriers of rare coding variants and in vitro in the supernatants of epithelial cells expressing recombinant FI. FI levels were measured in 177 plasma samples of 155 individuals, carrying 24 different rare coding variants in CFI. In carriers of the variants p.Gly119Arg, p.Leu131Arg, p.Gly188Ala and c.772G>A (r.685_773del), significantly reduced FI plasma levels were detected. Furthermore, recombinant FI expression levels were determined for 126 rare coding variants. Of these variants 68 (54%) resulted in significantly reduced FI expression in supernatant compared to wildtype (WT). The recombinant protein expression levels correlated significantly with the FI level in plasma of carriers of CFI variants. In this study, we performed the most comprehensive FI expression level ana...Continue Reading

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Citations

Feb 22, 2021·Progress in Retinal and Eye Research·Sarah de JongAnneke I den Hollander
May 20, 2021·Journal of Paediatrics and Child Health·Matthew D WongClaire E Wainwright
Jun 24, 2021·Investigative Ophthalmology & Visual Science·John T DemirsSha-Mei Liao
Aug 23, 2021·Cellular and Molecular Life Sciences : CMLS·Tess A V AfanasyevaRob W J Collin

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
biopsy
chip
PCR

Software Mentioned

GraphPad
SPSS Statistics
GraphPad Prism

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