Pcsk9 In African Americans And Caucasians In Relation To Lp(A) Level, Apo(A) Size And Heritability

Context: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces lipoprotein(a) [Lp(a)] levels, but the association of PCSK9 with Lp(a) level and its major determinant, apolipoprotein(a) [apo(a)] size, is not fully understood.Objective: To assess the relationship between PCSK9, Lp(a) level, apo(a) size, age, and ethnicity/ race.Design: Cross-sectionalSetting: General populationParticipants: Healthy African Americans and Caucasians (n = 267); age range: 6 to 74 years.Interventions: None.Main outcome measure(s): PCSK9 levels, apo(a) isoform and LPA allele sizes, and isoform-specific Lp(a) levels.Results: Plasma PCSK9 levels were significantly higher in African Americans vs Caucasians, in females vs males, and in adults vs children. PCSK9 levels were not associated with total plasma Lp(a) levels either in all participants or in ethnicity-specific analyses. However, PCSK9 levels were significantly positively associated with isoform-specific Lp(a) levels carried by the larger apo(a) size in all participants (r = 0.139, P= 0.0361). In ethnicity/race analyses, a significant association was seen for African Americans (r = 0.268, P= 0.0199), but not for Caucasians. In contrast, there were no significant associations of PCSK9 with isoform-specific Lp(a) levels for the smaller apo(a) sizes in all participants nor in ethnic-specific analyses. Furthermore, heritability (h(2)) analyses revealed a significant heritability for PCSK9 level in both ethnic groups, with a higher estimate in Caucasians than in African Americans (47% vs 22%, respectively).Conclusions: Among African Americans, but not Caucasians, PCSK9 levels were associated with isoform-specific Lp(a) levels carried on larger, but not smaller, apo(a) sizes. The findings illustrate a diverging relationship of PCSK9 with isoform-specific Lp(a) levels across ethnicity. (C) Endocrine Society 2020.