Sex and statin-related genetic associations at the PCSK9 gene locus: results of genome-wide association meta-analysis

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained b...

Full description

Saved in:
Bibliographic Details
Published in:Biology of sex differences 2024-03, Vol.15 (1), p.26-18, Article 26
Main Authors: Pott, Janne, Kheirkhah, Azin, Gadin, Jesper R, Kleber, Marcus E, Delgado, Graciela E, Kirsten, Holger, Forer, Lukas, Hauck, Stefanie M, Burkhardt, Ralph, Scharnagl, Hubert, Loeffler, Markus, März, Winfried, Thiery, Joachim, Gieger, Christian, Peters, Annette, Silveira, Angela, Hooft, Ferdinand Van't, Kronenberg, Florian, Scholz, Markus
Format: Article
Language:English
Subjects:
Analysis
Anticholesteremic agents
Antilipemic agents
Cholesterol
Drug dosages
Genes
Genetics
Genomes
Genomics
GWAS
High density lipoprotein
Interaction
Kexin
Lipid metabolism
Lipids
Lipoproteins
Low density lipoprotein
Low density lipoproteins
Medicin och hälsovetenskap
Meta-analysis
Metabolism
Missense mutation
Nitric-oxide synthase
PCSK9
Physiological aspects
Plasma levels
Proprotein convertases
Proteins
Sex
Sexual dimorphism
Statin
Statins
Subtilisin
Women
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics. We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups. We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p 
ISSN:2042-6410
2042-6410
DOI:10.1186/s13293-024-00602-6