Combined hyperlipidemia (CHL) was found to be similar genetically to isolated hypertriglyceridemia (HTG), according to a study published in the Journal of Clinical Lipidology.
Researchers sought to characterize the genetic profiles of patients with CHL and compare them with the profiles in patients with isolated hypercholesterolemia and isolated HTG. Targeted sequencing was conducted on DNA from 259 patients with CHL (mean age, 51.5±13.8 years; 44% women), 379 patients with isolated hypercholesterolemia (mean age, 57±17.8 years; 54% women), and 124 patients with isolated HTG (mean age, 59.9±13.4 years; 31% women).
The investigators assessed rare variants disrupting canonical low-density lipoprotein cholesterol (LDL-C) or triglyceride (TG) metabolism genes and 2 polygenic scores for elevated LDL-C and TG that were calculated using common trait-associated single-nucleotide polymorphisms (SNPs). The genetic profiles were compared with 1000 Genomes Project controls.
Patients with CHL and isolated HTG were found to have increased odds of a high polygenic score for TG: 2.50 (95% CI, 1.61-3.88; P <.001) and 3.72 (95% CI, 2.24-6.19; P <.001), respectively.
Patients with CHL did not have significant accumulation of rare variants for LDL-C or TG or a high polygenic score for LDL-C. Patients with isolated hypercholesterolemia had a 3.03-fold greater risk of carrying rare variants associated with familial hypercholesterolemia (95% CI, 2.22-4.13; P <.001), and those with isolated HTG had a 2.78-fold greater risk of carrying rare variants associated with severe HTG (95% CI, 1.27-6.10; P =.0136).
“Our targeted sequencing panel allows for simultaneous evaluation of DNA samples from [patients with] dyslipidemia for rare variants, including [copy number variants], and common variants bundled into a polygenic score,” noted the researchers. “Application of our panel in this study indicates that CHL most closely resembles isolated HTG at the genetic level, with both cohorts primarily showing a significantly increased likelihood of having a high polygenic score for TG…. The findings show that the genetic basis for CHL is polygenic, and further that it resembles the polygenic susceptibility seen in patients with isolated HTG.”
Study limitations include the fact that the 1000 Genomes Project cohort has no lipid information available, and some participants may have moderately elevated LDL-C. Also, the DNA of control individuals and patients were sequenced on different platforms and variants were determined using different algorithms.
“The elevated LDL-C component in our [participants with] CHL remains to be explained but is likely related to unmeasured variables,” the investigators commented. “Our results support the idea that CHL is genetically distinct from isolated hypercholesterolemia.”
Disclosures: One of the study authors reported affiliations with pharmaceutical companies. Please see the original reference for a full list of disclosures.
Gill PK, Dron JS, Berberich AJ, et al. Combined hyperlipidemia is genetically similar to isolated hypertriglyceridemia [published online November 23, 2020]. J Clin Lipidol. doi: 10.1016/j.jacl.2020.11.006