National Lipid Association
National Lipid Association
June 30, 2015
1 min read

Genetic variant reduces coronary events, increases diabetes risk in familial hypercholesterolemia

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CHICAGO — A PCSK9 loss-of-function genetic variant was associated with a cardioprotective effect, but increased prevalence of diabetes and prediabetes in patients with familial hypercholesterolemia, according to results presented at the National Lipid Association Scientific Sessions.

Researchers performed genotyping in 724 patients with familial hypercholesterolemia and established the presence of the PCSK9 InsLEU genetic variant to determine its potential link to diabetes, glucose homeostasis and coronary events.

The variant was identified in 26% of the cohort; of those, 24.2% were heterozygote carriers and 1.8% were homozygote or compound heterozygous carriers. The researchers found no significant difference between carriers and noncarriers in lipid profile or other baseline characteristics, including age, BMI, BP and hypertension.

Coronary events including MI, angina, stenting and CABG were less frequent among patients with the variant compared with noncarriers (30.6% vs. 22.1%; P = .04). The difference between noncarriers and carriers was more pronounced among homozygote or compound heterozygote carriers.

The rate of diabetes and prediabetes was higher among carriers of the genetic variant compared with noncarriers (10% vs. 6%; P = .04); however, the same trend was not observed when the rates of diabetes or prediabetes were individually evaluated. Patients with the variant also had higher concentrations of plasma glucose (5.3 mmol/L vs. 5.1 mmol/L; P = .02) and a higher frequency of impaired fasting glucose (31.3% vs. 14.3%; P < .01), particularly among homozygote or compound heterozygote carriers. Sex-specific analyses indicated that the difference in glucose concentration was only significant among women carrying the InsLEU variant (5.23 mmol/L vs. 4.99 mmol/L among noncarrier women; P = .04).

“This mutation is associated with decreased secretion of PCSK9, has minimal effect on the lipid profile [and] is cardioprotective, but unfortunately appears to be associated with dysglycemia and increased prediabetes and diabetes,” Y.G. Luna Saavedra, PhD, of the division of experimental medicine at McGill University, said during a presentation. – by Adam Taliercio


Saavedra YL, et al. Abstract #111. Presented at: National Lipid Association Scientific Sessions; June 11-14, 2015; Chicago.

Disclosure: Leducq Foundation funded the study. Saavedra reports no relevant financial disclosures.