Alayash Z, Baumeister S-E, Holtfreter B et al. Complement C3 as a potential drug target in periodontitis: Evidence from the cis-Mendelian randomization approach. J Clin Periodontol 2023; DOI: 10.1111/jcpe.13894.

Findings suggest a potential protective effect of C3 blockade against periodontitis.

Evidence from a Phase IIa trial showed that a complement C3-targeted drug reduced gingival inflammation in patients with gingivitis. Using drug-target Mendelian randomisation (MR), this study investigated whether genetically proxied C3 inhibition altered the risk of periodontitis. Multiple ‘cis' instruments from the vicinity of the encoding loci of C3 were used. Instrument selection was restricted to the drug target encoding loci. Three uncorrelated single-nucleotide polymorphisms associated with serum C3 levels were selected from a genome-wide association study (GWAS) of 5368 European descent individuals. Association statistics from a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls were extracted. MR analysis revealed that the inhibition of C3 reduces the odds of periodontitis.