Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/38898
Title: | Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review | Authors: | Van Dijck, Evelien Beckers, Sigri Diels, Sara Huybrechts, Tammy Verrijken, An Van Hoorenbeeck, Kim Verhulst, Stijn MASSA, Guy Van Gaal, Luc Van Hul, Wim |
Issue Date: | 2022 | Publisher: | MDPI | Source: | Genes, 13 (10) (Art N° 1746) | 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. | 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. wim.vanhul@uantwerpen.be |
Keywords: | proprotein convertase subtilisin;kexin type 1 (PCSK1);rare variants;founder mutation;obesity;overweight | Document URI: | http://hdl.handle.net/1942/38898 | e-ISSN: | 2073-4425 | DOI: | 10.3390/genes13101746 | ISI #: | 000873407600001 | 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/). | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
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 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.