Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.
Genes (Basel)
; 13(10)2022 Sep 27.
Article
em En
| MEDLINE
| ID: mdl-36292633
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_000439.5c.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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pró-Proteína Convertase 1
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Obesidade
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Child
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Humans
Idioma:
En
Revista:
Genes (Basel)
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Bélgica