Mutation Screening of the APOA5 Gene in Subjects With Coronary Artery Disease

作者：Soufi Muhidien^*; Sattler Alexander M; Kurt Bilgen; Schaefer Juergen R

来源：Journal of Investigative Medicine, 2012, 60(7): 1015-1019.

DOI：10.2310/JIM.0b013e3182686918

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

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%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;Results: APOA5 p.S19W variant c.56 C%26gt;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%26gt;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 %26lt; 0.01). %26lt;br%26gt;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.

• 出版日期2012-10