Assessing the safety of lipid-modifying medications among Chinese adolescents: a drug-target Mendelian randomization study.
BMC Med
; 21(1): 410, 2023 10 31.
Article
in En
| MEDLINE
| ID: mdl-37904165
ABSTRACT
BACKGROUND:
With increasing hypercholesterolemia prevalence in East Asian adolescents, pharmacologic interventions (e.g., HMGCR inhibitors (statins) and PCSK9 inhibitors) may have to be considered although their longer-term safety in the general adolescent population is unclear. This study aims to investigate the longer-term safety of HMGCR inhibitors and PCSK9 inhibitors among East Asian adolescents using genetics.METHODS:
A drug-target Mendelian randomization study leveraging the Global Lipid Genetics Consortium (East Asian, n = 146,492) and individual-level data from Chinese participants in the Biobank clinical follow-up of Hong Kong's "Children of 1997" birth cohort (n = 3443, aged ~ 17.6 years). Safety outcomes (n = 100) included anthropometric and hematological traits, renal, liver, lung function, and other nuclear magnetic resonance metabolomics. Positive control outcomes were cholesterol markers from the "Children of 1997" birth cohort and coronary artery disease from Biobank Japan.RESULTS:
Genetic inhibition of HMGCR and PCSK9 were associated with reduction in cholesterol-related NMR metabolomics, e.g., apolipoprotein B (HMGCR beta [95% CI], - 1.06 [- 1.52 to - 0.60]; PCSK9 - 0.93 [- 1.56 to - 0.31]) and had the expected effect on the positive control outcomes. After correcting for multiple comparisons (p-value < 0.006), genetic inhibition of HMGCR was associated with lower linoleic acid - 0.79 [- 1.25 to - 0.35]. Genetic inhibition of PCSK9 was not associated with the safety outcomes assessed.CONCLUSIONS:
Statins and PCSK9 inhibitors in East Asian adolescents appeared to be safe based on the outcomes concerned. Larger studies were warranted to verify these findings. This study serves as a proof of principle study to inform the medication safety among adolescents via genetics.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Limits:
Adolescent
/
Aged
/
Child
/
Humans
Language:
En
Journal:
BMC Med
Journal subject:
MEDICINA
Year:
2023
Document type:
Article
Affiliation country:
China