CYP11B1 variants influence skeletal maturation via alternative splicing.
Details
Serval ID
serval:BIB_46540000AB04
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CYP11B1 variants influence skeletal maturation via alternative splicing.
Journal
Communications biology
ISSN
2399-3642 (Electronic)
ISSN-L
2399-3642
Publication state
Published
Issued date
09/11/2021
Peer-reviewed
Oui
Volume
4
Number
1
Pages
1274
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
We performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; β = 0.14; P = 6.2 × 10 <sup>-12</sup> ). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10 <sup>-40</sup> ), exon 4 inclusion (P = 4.29 × 10 <sup>-34</sup> ), and decreased exon 3 and 5 splicing (P = 7.85 × 10 <sup>-43</sup> ), replicated using RT-PCR in 15 adrenal samples. As CYP11B1 encodes 11-β-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism.
Keywords
Age Determination by Skeleton, Alternative Splicing, Bone Development/genetics, Child, Female, Humans, Male, Steroid 11-beta-Hydroxylase/genetics, Steroid 11-beta-Hydroxylase/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
15/11/2021 14:42
Last modification date
08/08/2024 6:32