Plasma PCSK9 Is Associated with Age, Sex, and Multiple Metabolic Markers in a Population-Based Sample of Children and Adolescents

Abstract

BACKGROUND:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein convertase that posttranslationally promotes the degradation of the low-density lipoprotein receptor (LDLR) in hepatocytes and increases plasma LDL cholesterol (LDL-C). Heterozygote gain-of-function mutations of PCSK9 are associated with the familial hypercholesterolemia phenotype, whereas loss-of-function variants are associated with reduced LDL-C concentrations and lower coronary risk. Plasma PCSK9 correlates with body mass index, triglyceridemia, total cholesterol, and LDL-C in adults, but no data are available in youth.

Pcsk9

“…In contrast, in girls, PCSK9 levels peaked at the age of 13 years and then decreased to higher levels than boys at 16 years, and total cholesterol levels were higher in 9 and 16 years olds than in 13 years olds. 119 It is thought that this regulation follows a growth hormone pattern. 119 In the multiethnic Dallas Heart Study of 3138 patients, plasma PCSK9 levels were significantly higher in women (n=1863) than in men (n=1489).…”

“…119 It is thought that this regulation follows a growth hormone pattern. 119 In the multiethnic Dallas Heart Study of 3138 patients, plasma PCSK9 levels were significantly higher in women (n=1863) than in men (n=1489). This difference persisted after adjusting for most variables.. 120 In the same study, premenopausal women had considerably higher levels of plasma PCSK9 than postmenopausal women.…”

PCSK9: A key factor modulating atherosclerosis

“…Identifying the correlations between plasma PCSK9 levels and lipid and nonlipid risk factors supports the hypothesis that PCSK9 may have a broader physiological role in the vascular system. Recent reports on blacks, nonhispanic whites, Canadians, and the Han Chinese population have revealed that several demographic and metabolic parameters, including age, glucose, obesity or body mass index (BMI), and blood pressure are positively correlated with PCSK9 level [41][42][43] . It is well recognized that diabetes is associated with accelerated atherosclerosis.…”

“…Importantly, these mutations may be chronic hyperglycemia 45) . Circulating PCSK9 is positively correlated with fasting blood glucose levels and the homeostasis model assessment of insulin resistance, an index of insulin sensitivity, in several cohorts of n ondiabetic subjects [41][42][43] . However, inhibiting PCSK9 with an mAb in clinical studies did not significantly alter glucose metabolism.…”

New Frontiers in the Treatment of Diabetic Dyslipidemia

“…Inhibiting PCSK9 can potentially treat hypercholesterolemia [46]. PCSK-9 activity is associated with fasting insulinemia, postprandial lipid metabolism, and the hormonal control of lipids by estrogens, androgens, and growth hormone [47]. 209 (Novartis, Basel, Switzerland).…”