Universität zu Köln

de Jong, Sarah ORCID: 0000-0002-3705-3371, de Breuk, Anita, Volokhina, Elena B., Bakker, Bjorn, Garanto, Alejandro ORCID: 0000-0001-5721-1560, Fauser, Sascha, Katti, Suresh, Hoyng, Carel B., Lechanteur, Yara T. E., van den Heuvel, Lambert P. and den Hollander, Anneke, I (2022). Systemic complement levels in patients with age-related macular degeneration carrying rare or low-frequency variants in the CFH gene. Hum. Mol. Genet., 31 (3). S. 455 - 471. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2083

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Abstract

Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. Genetic variants in the complement factor H (CFH) gene are associated with AMD, but the functional consequences of many of these variants are currently unknown. In this study, we aimed to determine the effect of 64 rare and low-frequency variants in the CFH gene on systemic levels of factor H (FH) and complement activation marker C3bBbP using plasma samples of 252 carriers and 159 non-carriers. Individuals carrying a heterozygous nonsense, frameshift or missense variant in CFH presented with significantly decreased FH levels and significantly increased C3bBbP levels in plasma compared to non-carrier controls. FH and C3bBbP plasma levels were relatively stable over time in samples collected during follow-up visits. Decreased FH and increased C3bBbP concentrations were observed in carriers compared to non-carriers of CFH variants among different AMD stages, with the exception of C3bBbP levels in advanced AMD stages, which were equally high in carriers and non-carriers. In AMD families, FH levels were decreased in carriers compared to non-carriers, but C3bBbP levels did not differ. Rare variants in the CFH gene can lead to reduced FH levels or reduced FH function as measured by increased C3bBbP levels. The effects of individual variants in the CFH gene reported in this study will improve the interpretation of rare and low-frequency variants observed in AMD patients in clinical practice.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code de Jong, Sarah UNSPECIFIED orcid.org/0000-0002-3705-3371 UNSPECIFIED de Breuk, Anita UNSPECIFIED UNSPECIFIED UNSPECIFIED Volokhina, Elena B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bakker, Bjorn UNSPECIFIED UNSPECIFIED UNSPECIFIED Garanto, Alejandro UNSPECIFIED orcid.org/0000-0001-5721-1560 UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Katti, Suresh UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lechanteur, Yara T. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Heuvel, Lambert P. UNSPECIFIED UNSPECIFIED UNSPECIFIED den Hollander, Anneke, I UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-676183
DOI:	10.1093/hmg/ddab256
Journal or Publication Title:	Hum. Mol. Genet.
Volume:	31
Number:	3
Page Range:	S. 455 - 471
Date:	2022
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2083
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEMOLYTIC-UREMIC SYNDROME; MEMBRANE ATTACK COMPLEX; H-LIKE PROTEIN-1; FUNCTIONAL-CHARACTERIZATION; ACTIVATION; MUTATIONS; MACULOPATHY; DISEASE; ASSOCIATIONS; REGULATOR Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67618