Longitudinal association of pcsk9 sequence variations with low-density lipoprotein cholesterol levels: The coronary artery risk development in young adults study

Chiang Ching Huang, Myriam Fornage, Donald M. Lloyd-Jones, Gina S. Wei, Eric Boerwinkle, Kiang Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Background-Mutations of PCSK9 are associated cross-sectionally with plasma low-density lipoprotein cholesterol (LDL-C) levels, but little is known about their longitudinal association with LDL-C levels from young adulthood to middle age. Methods and Results-We investigated the associations of 6 PCSK9 variants with LDL-C over 20 years in 1750 blacks and 1828 whites from the Coronary Artery Risk Development In Young Adults study. Generalized estimating equations were used to assess longitudinal differences in LDL-C levels between genotype categories. For blacks, LDL-C levels at age 18 were significantly lower (P<0.001) among those with 3 genetic variants (L253F, C679X, and Y142X; 81.5 mg/dL) and A443T (95.5 mg/dL) compared with noncarriers (109.6 mg/dL). The difference in LDL-C levels from noncarriers tended to widen for those with the 3 variants only, by 0.24 mg/dL per year of age (P=0.14). For whites with the R46L variant, compared with noncarriers, LDL-C levels at age 18 were significantly lower (84.4 mg/dL versus 100.9 mg/dL; P<0.001), and the increase in LDL-C with age was similar to noncarriers. The 3 genetic variants and the A443T variant in black men were associated with lower carotid intima-media thickness and lower prevalence of coronary calcification measured at ages 38 to 50. Conclusions-Our results suggest that participants with several genetic variants of PCSK9 have persistently lower serum LDL-C levels than noncarriers from ages 18 to 50. Such long-term reduction in LDL-C levels is associated with reduced subclinical atherosclerosis burden in black men.

Original languageEnglish (US)
Pages (from-to)354-361
Number of pages8
JournalCirculation: Cardiovascular Genetics
Volume2
Issue number4
DOIs
StatePublished - Aug 2009

Keywords

  • Genetic variant
  • LDL-C
  • Longitudinal study
  • PCSK9
  • Words

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Longitudinal association of pcsk9 sequence variations with low-density lipoprotein cholesterol levels: The coronary artery risk development in young adults study'. Together they form a unique fingerprint.

Cite this