rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography

Nutr Metab Cardiovasc Dis. 2021 May 6;31(5):1542-1547. doi: 10.1016/j.numecd.2021.01.018. Epub 2021 Feb 3.

Abstract

Background and aims: Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients.

Methods and results: The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG. The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04-1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04-1.96) and 1.39 (1.22-1.58) respectively].

Conclusions: rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.

Keywords: Apolipoproteins; Coronary artery disease; Gene polymorphism; Lipids; Sortilin.

Publication types

  • Meta-Analysis
  • Multicenter Study

MeSH terms

  • Age Factors
  • Aged
  • Biomarkers / blood
  • Cadherins / genetics*
  • Coronary Angiography*
  • Coronary Stenosis / blood
  • Coronary Stenosis / diagnostic imaging*
  • Coronary Stenosis / epidemiology
  • Coronary Stenosis / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Italy / epidemiology
  • Lipids / blood
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors

Substances

  • Biomarkers
  • CELSR2 protein, human
  • Cadherins
  • Lipids