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Genotype‐driven NPC1L1 and PCSK9 inhibition and reduced risk of periodontitis
Author(s) -
Baumeister SebastianEdgar,
Holtfreter Birte,
Reckelkamm Stefan Lars,
Kocher Thomas,
Alayash Zoheir,
Ehmke Benjamin,
Baurecht Hansjörg,
Nolde Michael
Publication year - 2023
Publication title -
journal of clinical periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.456
H-Index - 151
eISSN - 1600-051X
pISSN - 0303-6979
DOI - 10.1111/jcpe.13719
Subject(s) - pcsk9 , periodontitis , odds ratio , medicine , statin , ezetimibe , gastroenterology , endocrinology , cholesterol , lipoprotein , ldl receptor
Aim Epidemiological and pre‐clinical studies suggest a chemoprotective role of lipid‐lowering agents in periodontitis. We tested the association of genetically proxied inhibition of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGCR), Niemann‐Pick C1‐Like 1 ( NPC1L1 ) and proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) with periodontitis. Materials and Methods Genetic variants in HMGCR , NCP1L1 and PCSK9 associated with low‐density lipoprotein (LDL) cholesterol in a genome‐wide association study (GWAS) meta‐analysis ( N = 188,578) were used to proxy therapeutic inhibition of HMGCR, NPC1L1 and PCSK9. For these genetic variants, associations with periodontitis were obtained from GWAS of 17,353 cases and 28,210 controls in the GeneLifestyle Interactions in Dental Endpoints consortium. Generalized weighted least squares analysis accounted for linkage disequilibrium of genotypes to derive pooled estimates. Results While genetically proxied HMGCR inhibition equivalent to 1 mmol/L reduction in LDL was not associated with odds of periodontitis (odds ratio [OR] = 0.92 [95% confidence interval [CI]: 0.73; 1.16]; p = .4905; false discovery rate [FDR] = 0.4905), genetically proxied NPC1L1 (OR = 0.53 [95% CI: 0.35; 0.81]; p = .0038; FDR = 0.0077) and PCSK9 (OR = 0.84 [95% CI: 0.74; 0.95]; p = .0051; FDR = 0.0077) inhibition lowered the odds of periodontitis. Conclusions Genetically proxied inhibition of NCP1L1 and PCSK9 was associated with lower odds of periodontitis.