Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jul;33(7):1521-8.
doi: 10.1161/ATVBAHA.113.301505. Epub 2013 May 16.

Evidence of a polygenic origin of extreme high-density lipoprotein cholesterol levels

Mohammad Mahdi Motazacker  1 , Jorge Peter, Marco Treskes, Carol C Shoulders, Jan Albert Kuivenhoven, G Kees Hovingh
Affiliations

Evidence of a polygenic origin of extreme high-density lipoprotein cholesterol levels

Mohammad Mahdi Motazacker et al. Arterioscler Thromb Vasc Biol. 2013 Jul.

Erratum in

  • Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):e128

Abstract

Objective: There are several known monogenic causes of high and low high-density lipoprotein cholesterol (HDL-C) levels, but traditional sequencing studies have had limited success in identifying mutations in the majority of individuals with extreme HDL-C levels. The aim of this study was to assess the power of a targeted high-throughput sequencing strategy to elucidate the genetic basis of extreme HDL-C phenotypes.

Approach and results: We sequenced 195 genes with either established or implicated roles in lipid and lipoprotein metabolism plus 78 lipid-unrelated genes in patients with HDL-C <1st (n=40) or >99th (n=40) percentile values, and the results were compared with those of 498 individuals representative of the Dutch general population and 95 subjects with normal HDL-C (between 40th and 60th percentile values). The extreme HDL cohort carried more rare nonsynonymous variants in the lipid geneset than both the general population (odds ratio, 1.39; P=0.019) and normal HDL-C (odds ratio, 1.43; P=0.040) cohorts. The prevalence of such variants in the lipid-related and lipid-unrelated genesets was similar in the control groups, indicative of equal mutation rates. In the extreme HDL cohort, however, there was enrichment of rare nonsynonymous variants in the lipid versus the control geneset (odds ratio, 2.23; P<0.0001), and 70% of the lipid-related variants altered conserved nucleotides. The lipid geneset comprised 4 nonsense, 10 splice-site, and 8 coding indel variants, whereas the control geneset contained only 1 such variant. In the lipid geneset, 87% and 28% of the patients carried ≥ 2 and ≥ 5 rare variants.

Conclusions: This study suggests that most extreme HDL-C phenotypes have a polygenic origin.

Keywords: genetic variation; high-density lipoprotein cholesterol; lipid metabolism; low-density lipoprotein cholesterol; polygenic traits; triglycerides.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources