Mutation screening of the APOA5 gene in subjects with coronary artery disease.
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.
Department of Internal Medicine, Cardiology, Philipps University, Marburg, Germany. soufi@staff.uni-marburg.de
Muhidien
M
Soufi
Alexander M
AM
Sattler
Bilgen
B
Kurt
Juergen R
JR
Schaefer
D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008074:Lipoproteins