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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary

Gina M Peloso1, Serkalem Demissie, Dorothea Collins

  • 1Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

Journal of Lipid Research
|September 22, 2010
PubMed

Insights

This study identified genetic variants linked to low HDL cholesterol and coronary heart disease risk. Novel susceptibility alleles were found in CUBN and RXRA genes, with SELP variation potentially impacting HDL

Area of Science:

  • Genetics and Cardiovascular Disease
  • Lipid Metabolism and Atherosclerosis

Background:

  • Low high-density lipoprotein cholesterol (HDL-C) is a prevalent lipid abnormality in men with established coronary heart disease (CHD).
  • Identifying genetic factors influencing HDL-C levels and CHD susceptibility is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To identify allelic variants associated with susceptibility to low HDL-C and CHD.
  • To investigate the roles of candidate genes in HDL metabolism, insulin resistance, and inflammation.

Main Methods:

  • Examined 60 candidate genes involved in HDL metabolism, insulin resistance, and inflammation.
  • Utilized genetic data from the Veterans Affairs HDL Intervention Trial (VA-HIT) and the Framingham Offspring Study (FOS).
  • Employed single-nucleotide polymorphism (SNP) analysis with adjustments for multiple testing.

Main Results:

  • Significant SNPs associated with case status were identified in LIPC, CETP, RXRA, ABCA1, ABCC6, CUBN, APOA2, SELP, and APOC4 genes.
  • Novel susceptibility alleles for low HDL-C/CHD risk were found in the CUBN and RXRA genes.
  • Genetic variation in SELP was observed to potentially influence CHD risk via its effects on HDL.

Conclusions:

  • Genetic variations in multiple genes, including novel associations in CUBN and RXRA, contribute to low HDL-C and CHD risk.
  • SELP gene variation represents a potential new pathway through which HDL influences CHD risk.
  • These findings enhance our understanding of the genetic underpinnings of dyslipidemia and cardiovascular disease.

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