title: Lipoprotein(a) in Familial Hypercholesterolemia With Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Gain-of-Function Mutations.
abstract: BACKGROUND
  It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mutation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene.
  
  
  RESULTS
  We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4-33.9], 21.1 mg/dl [IQR:11.7-34.9], and 5.0 mg/dl [IQR:2.7-8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL).
  
  
  CONCLUSIONS
  These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations.
authors.affiliation: Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine.
authors.forename: Hayato
authors.initials: H
authors.lastname: Tada
authors.forename: Masa-Aki
authors.initials: MA
authors.lastname: Kawashiri
authors.forename: Taiji
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ryota
authors.initials: R
authors.lastname: Teramoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nohara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Konno
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inazu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics*; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism
chemical_list: C573412:LDLR protein, human; D017270:Lipoprotein(a); D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases