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http://hdl.handle.net/1942/38898
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DC Field | Value | Language |
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dc.contributor.author | Van Dijck, Evelien | - |
dc.contributor.author | Beckers, Sigri | - |
dc.contributor.author | Diels, Sara | - |
dc.contributor.author | Huybrechts, Tammy | - |
dc.contributor.author | Verrijken, An | - |
dc.contributor.author | Van Hoorenbeeck, Kim | - |
dc.contributor.author | Verhulst, Stijn | - |
dc.contributor.author | MASSA, Guy | - |
dc.contributor.author | Van Gaal, Luc | - |
dc.contributor.author | Van Hul, Wim | - |
dc.date.accessioned | 2022-11-21T10:51:18Z | - |
dc.date.available | 2022-11-21T10:51:18Z | - |
dc.date.issued | 2022 | - |
dc.date.submitted | 2022-11-18T12:09:22Z | - |
dc.identifier.citation | Genes, 13 (10) (Art N° 1746) | - |
dc.identifier.uri | http://hdl.handle.net/1942/38898 | - |
dc.description.abstract | Recently, it was reported that heterozygous PCSK1 variants, causing partial PC1/3 deficiency, result in a significant increased risk for obesity. This effect was almost exclusively generated by the rare p.Y181H (rs145592525, GRCh38.p13 NM_000439.5:c.541T>C) variant, which affects PC1/3 maturation but not enzymatic capacity. As most of the identified individuals with the heterozygous p.Y181H variant were of Belgian origin, we performed a follow-up study in a population of 481 children and adolescents with obesity, and 486 lean individuals. We identified three obese (0.62%) and four lean (0.82%) p.Y181H carriers (p = 0.506) through sanger sequencing and high resulting melting curve analysis, indicating no association with obesity. Haplotype analysis was performed in 13 p.Y181H carriers, 20 non-carriers (10 with obesity and 10 lean), and two p.Y181H families, and showed identical haplotypes for all heterozygous carriers (p < 0.001). Likewise, state-of-the-art literature concerning the role of rare heterozygous PCSK1 variants implies them to be rarely associated with monogenic obesity, as first-degree carrier relatives of patients with PC1/3 deficiency are mostly not reported to be obese. Furthermore, recent meta-analyses have only indicated a robust association for scarce disruptive heterozygous PCSK1 variants with obesity, while clinical significance is less or sometimes lacking for most nonsynonymous variants. | - |
dc.description.sponsorship | This research was funded by a Methusalem-OEC grant—“GENOMED” (Grant Number: FFB190208). Evelien Van Dijck is supported by a GOA-grant (FFB180348/36572) and a FWO-grant (Fonds Wetenschappelijk Onderzoek) (Grant Number: 11E6921N). The Methusalem-OEC grant and the GOA-grant are both from the University of Antwerp. The APC was funded by a grant from the university of Antwerp to WVH. | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.rights | 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). | - |
dc.subject.other | proprotein convertase subtilisin | - |
dc.subject.other | kexin type 1 (PCSK1) | - |
dc.subject.other | rare variants | - |
dc.subject.other | founder mutation | - |
dc.subject.other | obesity | - |
dc.subject.other | overweight | - |
dc.title | Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review | - |
dc.type | Journal Contribution | - |
dc.identifier.issue | 10 | - |
dc.identifier.volume | 13 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Van Hul, W (corresponding author), Univ Antwerp, Ctr Med Genet, B-2650 Edegem, Belgium.; Van Hul, W (corresponding author), Antwerp Univ Hosp, B-2650 Edegem, Belgium. | - |
dc.description.notes | wim.vanhul@uantwerpen.be | - |
local.publisher.place | ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND | - |
local.type.refereed | Refereed | - |
local.type.specified | Review | - |
local.bibliographicCitation.artnr | 1746 | - |
local.class | dsPublValOverrule/no_publishing_delay | - |
dc.identifier.doi | 10.3390/genes13101746 | - |
dc.identifier.isi | 000873407600001 | - |
local.provider.type | wosris | - |
local.description.affiliation | [Van Dijck, Evelien; Beckers, Sigri; Diels, Sara; Huybrechts, Tammy; Van Hul, Wim] Univ Antwerp, Ctr Med Genet, B-2650 Edegem, Belgium. | - |
local.description.affiliation | [Van Dijck, Evelien; Beckers, Sigri; Diels, Sara; Huybrechts, Tammy; Van Hul, Wim] Antwerp Univ Hosp, B-2650 Edegem, Belgium. | - |
local.description.affiliation | [Verrijken, An; Van Gaal, Luc] Antwerp Univ Hosp, Dept Endocrinol Diabetol & Metab Dis, B-2650 Edegem, Belgium. | - |
local.description.affiliation | [Van Hoorenbeeck, Kim; Verhulst, Stijn] Antwerp Univ Hosp, Dept Pediat, B-2650 Edegem, Belgium. | - |
local.description.affiliation | [Massa, Guy] Jessa Hosp, Dept Pediat, B-3500 Hasselt, Belgium. | - |
local.uhasselt.international | no | - |
item.accessRights | Open Access | - |
item.fullcitation | Van Dijck, Evelien; Beckers, Sigri; Diels, Sara; Huybrechts, Tammy; Verrijken, An; Van Hoorenbeeck, Kim; Verhulst, Stijn; MASSA, Guy; Van Gaal, Luc & Van Hul, Wim (2022) Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review. In: Genes, 13 (10) (Art N° 1746). | - |
item.fulltext | With Fulltext | - |
item.contributor | Van Dijck, Evelien | - |
item.contributor | Beckers, Sigri | - |
item.contributor | Diels, Sara | - |
item.contributor | Huybrechts, Tammy | - |
item.contributor | Verrijken, An | - |
item.contributor | Van Hoorenbeeck, Kim | - |
item.contributor | Verhulst, Stijn | - |
item.contributor | MASSA, Guy | - |
item.contributor | Van Gaal, Luc | - |
item.contributor | Van Hul, Wim | - |
crisitem.journal.eissn | 2073-4425 | - |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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Rare Heterozygous PCSK1 Variants in Human Obesity_ The Contribution of the p.Y181H Variant and a Literature Review.pdf | Published version | 502.87 kB | Adobe PDF | View/Open |
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