Genetic determinants of quantitative traits associated with cardiovascular disease risk

Mutat Res. 2015 Aug:778:18-25. doi: 10.1016/j.mrfmmm.2015.05.005. Epub 2015 May 15.

Abstract

Established risk factors for cardiovascular diseases (CVD) may be moderated by genetic variants. In 2403 unrelated individuals from general practice (mean age 40.5 years), we evaluated the influence of 15 variants in 12 candidate genes on quantitative traits (QT) associated with CVD (body mass index, abdominal obesity, glucose, serum lipids, and blood pressure). Prior to multiple testing correction, univariate analysis associated APOE rs429358, rs7412 and ATG16L1 rs2241880 variants with serum lipid levels, while LEPR rs1137100 and ATG16L1 rs2241880 variants were linked to obesity related QTs. After taking into account confounding factors and correcting for multiple comparisons only APOE rs429358 and rs7412 variants remained significantly associated with risk of dyslipidemia. APOE rs429358 variant almost tripled the risk in homozygous subjects (OR = 2.97; 95% CI 1.09-8.10, p < 0.03) and had a lesser but still highly significant association also in heterozygous individuals (OR = 1.67; 95% CI 1.24-2.10; p < 0.001). Associations with hypertension, diabetes mellitus, and metabolic syndrome were not significant after Bonferroni correction. The influence of genetic variation is more evident in dyslipidemia than in other analyzed QTs. These results may contribute to strategic research aimed at including genetic variation in the set of data required to identify subjects at high risk of CVD.

Keywords: Candidate gene; Cardiovascular disease; Genetic susceptibility; Quantitative trait; Risk factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoproteins E / genetics
  • Autophagy-Related Proteins
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Carrier Proteins / genetics
  • Comorbidity
  • DNA / genetics
  • DNA / isolation & purification
  • Dyslipidemias / epidemiology
  • Dyslipidemias / genetics
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Hyperglycemia / epidemiology
  • Hyperglycemia / genetics
  • Hypertension / epidemiology
  • Hypertension / genetics
  • Male
  • Middle Aged
  • Obesity / epidemiology
  • Obesity / genetics
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • Receptors, Leptin / genetics
  • Risk
  • Risk Factors
  • Sequence Analysis, DNA
  • Slovakia / epidemiology
  • Waist Circumference

Substances

  • ATG16L1 protein, human
  • Apolipoproteins E
  • Autophagy-Related Proteins
  • Carrier Proteins
  • LEPR protein, human
  • Receptors, Leptin
  • DNA