Investigation of Complement Component C4 Copy Number Variation in Human Longevity

Genetic factors have been estimated to account for about 25% of the variation in an adult's life span. The complement component C4 with the isotypes C4A and C4B is an effector protein of the immune system, and differences in the overall C4 copy number or gene size (long C4L; short C4S) may infl...

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Main Authors:	Flachsbart, Friederike, Caliebe, Amke, Heinsen, Femke-Anouska, Hemming-Karlsen, Tom, Schreiber, Stefan, Franke, Andre, Nebel, Almut
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899116/

id	pubmed-3899116
recordtype	oai_dc
spelling	pubmed-38991162014-01-24 Investigation of Complement Component C4 Copy Number Variation in Human Longevity Flachsbart, Friederike Caliebe, Amke Heinsen, Femke-Anouska Hemming-Karlsen, Tom Schreiber, Stefan Franke, Andre Nebel, Almut Research Article Genetic factors have been estimated to account for about 25% of the variation in an adult's life span. The complement component C4 with the isotypes C4A and C4B is an effector protein of the immune system, and differences in the overall C4 copy number or gene size (long C4L; short C4S) may influence the strength of the immune response and disease susceptibilities. Previously, an association between C4B copy number and life span was reported for Hungarians and Icelanders, where the C4BQ0 genotype, which is defined by C4B gene deficiency, showed a decrease in frequency with age. Additionally, one of the studies indicated that a low C4B copy number might be a genetic trait that is manifested only in the presence of the environmental risk factor “smoking”. These observations prompted us to investigate the role of the C4 alleles in our large German longevity sample (∼700 cases; 94–110 years and ∼900 younger controls). No significant differences in the number of C4A, C4B and C4S were detected. Besides, the C4BQ0 carrier state did not decrease with age, irrespective of smoking as an interacting variable. However, for C4LQ0 a significantly different carrier frequency was observed in the cases compared with controls (cases: 5.08%; controls: 9.12%; p = 0.003). In a replication sample of 714 German cases (91–108 years) and 890 controls this result was not replicated (p = 0.14) although a similar trend of decreased C4LQ0 carrier frequency in cases was visible (cases: 7.84%; controls: 10.00%). Public Library of Science 2014-01-22 /pmc/articles/PMC3899116/ /pubmed/24465950 http://dx.doi.org/10.1371/journal.pone.0086188 Text en © 2014 Flachsbart et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Flachsbart, Friederike Caliebe, Amke Heinsen, Femke-Anouska Hemming-Karlsen, Tom Schreiber, Stefan Franke, Andre Nebel, Almut
spellingShingle	Flachsbart, Friederike Caliebe, Amke Heinsen, Femke-Anouska Hemming-Karlsen, Tom Schreiber, Stefan Franke, Andre Nebel, Almut Investigation of Complement Component C4 Copy Number Variation in Human Longevity
author_facet	Flachsbart, Friederike Caliebe, Amke Heinsen, Femke-Anouska Hemming-Karlsen, Tom Schreiber, Stefan Franke, Andre Nebel, Almut
author_sort	Flachsbart, Friederike
title	Investigation of Complement Component C4 Copy Number Variation in Human Longevity
title_short	Investigation of Complement Component C4 Copy Number Variation in Human Longevity
title_full	Investigation of Complement Component C4 Copy Number Variation in Human Longevity
title_fullStr	Investigation of Complement Component C4 Copy Number Variation in Human Longevity
title_full_unstemmed	Investigation of Complement Component C4 Copy Number Variation in Human Longevity
title_sort	investigation of complement component c4 copy number variation in human longevity
description	Genetic factors have been estimated to account for about 25% of the variation in an adult's life span. The complement component C4 with the isotypes C4A and C4B is an effector protein of the immune system, and differences in the overall C4 copy number or gene size (long C4L; short C4S) may influence the strength of the immune response and disease susceptibilities. Previously, an association between C4B copy number and life span was reported for Hungarians and Icelanders, where the C4BQ0 genotype, which is defined by C4B gene deficiency, showed a decrease in frequency with age. Additionally, one of the studies indicated that a low C4B copy number might be a genetic trait that is manifested only in the presence of the environmental risk factor “smoking”. These observations prompted us to investigate the role of the C4 alleles in our large German longevity sample (∼700 cases; 94–110 years and ∼900 younger controls). No significant differences in the number of C4A, C4B and C4S were detected. Besides, the C4BQ0 carrier state did not decrease with age, irrespective of smoking as an interacting variable. However, for C4LQ0 a significantly different carrier frequency was observed in the cases compared with controls (cases: 5.08%; controls: 9.12%; p = 0.003). In a replication sample of 714 German cases (91–108 years) and 890 controls this result was not replicated (p = 0.14) although a similar trend of decreased C4LQ0 carrier frequency in cases was visible (cases: 7.84%; controls: 10.00%).
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899116/
_version_	1612050232889049088

Investigation of Complement Component C4 Copy Number Variation in Human Longevity

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