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Mutation Screening of the APOA5 Gene in Subjects With Coronary Artery Disease
  1. Muhidien Soufi, PhD,
  2. Alexander M. Sattler, MD,
  3. Bilgen Kurt, MD,
  4. Juergen R. Schaefer, MD
  1. From the Department of Internal Medicine, Cardiology, Philipps University, Marburg, Germany.
  1. Received March 16, 2012, and in revised form July 3, 2012.
  2. Accepted for publication July 3, 2012.
  3. Reprints: Muhidien Soufi, PhD, Department of Internal Medicine–Cardiology, Philipps-Universität Marburg, D-35033 Marburg, Germany. E-mail: soufi{at}
  4. Supported by grants of the Dr Reinfried Pohl-Professorship Preventive Cardiology at the Philipps-Universität Marburg to JRS.


Objective Hyperlipidemia is a risk factor for coronary artery disease (CAD). Apolipoprotein A5 (APOA5) is a member of the apolipoprotein APOA1/C3/A4/A5 gene cluster and a major determinant of plasma triglyceride levels in the population. Various studies have identified a number of common (APOA5 c.56C>G; p.S19W; rs 3135506 ) and rare variants in the APOA5 gene in individuals with hypertriglyceridemia. However, little is known on the impact of rare APOA5 mutations for the risk of coronary artery disease; therefore, we screened the APOA5 gene in subjects with CAD.

Methods The coding region of the APOA5 gene was screened in 501 subjects (334 with CAD and 167 CAD-free) undergoing diagnostic coronary angiography by denaturing gradient gel electrophoresis.

Results APOA5 p.S19W variant c.56 C>G was found in a total of 61 subjects, five of them homozygous. Beside this well-known mutation, the denaturing gradient gel electrophoresis screening identified only one subject with a synonymous APOA5 mutation, c.70C>A; p.R24R. APOA5 p.S19W was more frequent in patients with CAD (CAD, 14.4%; no CAD, 7.8%; P = 0.021); and in addition, all homozygous subjects (n = 5) for APOA5 p.S19W had CAD. Furthermore, carriers of the p.19W allele had significantly higher triglyceride levels (240 ± 149 vs 185 ± 118 mg/dL; P < 0.01).

Conclusions From these data, we conclude that (1) APOA5 p.S19W is a common variant, with very few additional APOA5 gene mutations; (2) APOA5 p.S19W plays a major role in triglyceride metabolism; and (3) APOA5 p.S19W is a CAD risk factor.

Key Words
  • risk factor
  • coronary artery disease
  • apolipoprotein A5
  • hyperlipidemia
  • mutation screening

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