Complement C3 as a potential drug target in periodontitis: Evidence from the cis-Mendelian randomization approach.
J Clin Periodontol
; 51(2): 127-134, 2024 02.
Article
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| MEDLINE
| ID: mdl-37926509
ABSTRACT
AIM:
Evidence from a Phase IIa trial showed that a complement C3-targeted drug reduced gingival inflammation in patients with gingivitis. Using drug-target Mendelian randomization (MR), we investigated whether genetically proxied C3 inhibition alters the risk of periodontitis. MATERIALS ANDMETHODS:
We used multiple 'cis' instruments from the vicinity of the encoding loci of C3. Instrument selection was restricted to the drug target encoding loci (chromosome 19; 6,677,715-6,730,573 (GRCh37/hg19)). We selected three uncorrelated single-nucleotide polymorphisms (rs141552034, rs145406915, rs11569479) that were associated with serum C3 levels (p value <1 × 10-4 ) from a genome-wide association study (GWAS) of 5368 European descent individuals. We extracted association statistics from a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Wald ratios were combined using inverse-variance weighted meta-analysis to estimate the odds ratio (OR) of the genetically proxied inhibition of C3 in relation to periodontitis.RESULTS:
MR analysis revealed that the inhibition of C3 reduces the odds of periodontitis (OR 0.91 per 1 standard deviation reduction in C3; 95% confidence interval 0.87-0.96, p value = .0003).CONCLUSIONS:
Findings from our MR analysis suggest a potential protective effect of C3 blockade against periodontitis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Periodontitis
/
Gingivitis
Límite:
Humans
Idioma:
En
Revista:
J Clin Periodontol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania