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Different genes and polymorphisms affecting high-density lipoprotein cholesterol levels in Greek familial

George V Z Dedoussis1, Sandy Maumus, Despoina M Choumerianou

  • 1Laboratory of Molecular Biology, Department of Science of Dietetics-Nutrition, Harokopio University of Athens, Kallithea-Athens, Greece. dedousi@hua.gr

Genetic Testing
|October 6, 2006
PubMed

Insights

Genetic variants in APOCIII and ADRB2 influence high-density lipoprotein cholesterol (HDL-C) levels in Familial Hypercholesterolemia (FH) patients. These findings contribute to understanding FH variability and potential therapeutic targets.

Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Familial Hypercholesterolemia (FH) is an inherited disorder causing elevated low-density lipoprotein cholesterol (LDL-C) and premature coronary artery disease.
  • FH exhibits variable clinical presentation, even among individuals with identical LDL receptor gene mutations, suggesting contributions from other genetic and environmental factors.

Purpose of the Study:

  • To investigate the impact of specific genetic polymorphisms (APOCIII T1100C, FV Gln506Arg, ADRB2 Glu27Gln, SELE Ser128Arg, SELE Leu554Phe, ENaCa Ala663Thr) on high-density lipoprotein cholesterol (HDL-C) variations in 84 FH patients.
  • To identify genetic factors contributing to the heterogeneity of lipid profiles in FH.

Main Methods:

  • Genotyping of six selected polymorphisms in 84 patients diagnosed with FH.
  • Analysis of the association between each polymorphism and HDL-C levels using linear regression, adjusted for age and sex.
  • Evaluation of the influence of polymorphisms on other lipid parameters including total cholesterol, LDL-C, triglycerides, apolipoprotein A, apolipoprotein B, and lipoprotein alpha.

Main Results:

  • The APOCIII T1100C polymorphism was associated with higher HDL-C levels in subjects with the TT genotype (p = 0.046).
  • The Gln allele of the ADRB2 Glu27Gln polymorphism was linked to elevated HDL-C levels in heterozygotes and homozygotes (p = 0.014).
  • Linear regression models confirmed significant associations between HDL-C levels and polymorphisms ApoCIII T1100C, FV Gln506Arg, and ADRB2 Glu27Gln (p = 0.01, p = 0.018, p = 0.04, respectively).

Conclusions:

  • Specific genetic variants, notably APOCIII T1100C and ADRB2 Glu27Gln, significantly influence HDL-C concentrations in individuals with Familial Hypercholesterolemia.
  • These findings highlight the role of distinct genetic polymorphisms in modulating HDL-C levels, contributing to the variable clinical expression observed in FH heterozygotes.
  • Further research into these genetic associations may offer insights into personalized management strategies for FH.

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