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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Apolipoprotein E Genotype and Circulating Interleukin-10 Levels in Patients With Stable and Unstable Coronary Artery Disease

Dimitrios N. Tziakas, MD, PhD^_*,_*, Georgios K. Chalikias, MD, PhD^_*, Christos O. Antonoglou, MD, PhD, Stavroula Veletza, PhD, Ioannis K. Tentes, PhD, Alexandros X. Kortsaris, PhD, Dimitrios I. Hatseras, MD, PhD^_* and Juan Carlos Kaski, MD, DSc, FACC^||

^_* University Cardiology Department, Democritus University of Thrace, Alexandroupolis, Greece
2nd Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
Department of Medical Biology, Democritus University of Thrace, Alexandroupolis, Greece
Department of Biochemistry, Democritus University of Thrace, Alexandroupolis, Greece
^|| Cardiovascular Biology Research Centre, Division of Cardiac and Vascular Sciences, St. George’s, University of London, London, United Kingdom.

Manuscript received June 7, 2006; revised manuscript received July 31, 2006, accepted August 7, 2006.

^_* Reprint requests and correspondence: Dr. Dimitrios N. Tziakas, Voulgaroktonou 23, 68100 Alexandroupolis, Greece. (Email: dtziakas{at}med.duth.gr).

OBJECTIVES: This study was designed to assess the relation between apolipoprotein E (apoE) genotype and serum interleukin (IL)-10 levels in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA).

BACKGROUND: Genetic variations in the apoE gene affect the risk for coronary artery disease (i.e., carriers of the e4 allele have an increased risk). Increased levels of C-reactive protein (CRP), an inflammatory marker, correlate with an increased risk of acute coronary events, whereas increased IL-10 concentrations have an atheroprotective role. Studies have reported a negative association between the apoE e4 allele and CRP levels.

METHODS: Apolipoprotein E genotypes were assessed in 166 consecutive ACS patients (119 men, mean age 68 years, interquartile range [IQR] 60 to 74 years) and 70 CSA patients (54 men, mean age 65 years, IQR 62 to 68 years). Serum IL-10 and CRP were assessed at study entry.

RESULTS: Analysis of covariance showed that genetic variation in the apoE gene locus significantly influences serum IL-10 levels in both ACS (p = 0.009) and CSA patients (p = 0.013). Among ACS patients, IL-10 levels were lower in E3/E4 carriers compared with E3/E3 carriers (p = 0.01) and marginally lower compared with E2/E3 carriers (p = 0.065). Among CSA patients, IL-10 levels were lower in E3/E4 carriers compared with E2/E3 carriers (p = 0.004) and marginally lower compared with E3/E3 carriers (p = 0.086).

CONCLUSIONS: The IL-10 concentrations differ in ACS and in CSA patients with different apoE genotypes. The e4 allele was associated with a trend toward lower IL-10 serum levels. Our results may provide an explanation of findings in previous studies that cardiovascular risk is higher in e4 carriers despite the presence of low CRP levels.

Abbreviations and Acronyms   ANCOVA = analysis of covariance   apoE = apolipoprotein E   CAD = coronary artery disease   CRP = C-reactive protein   CSA = chronic stable angina   HDL = high-density lipoprotein   IL = interleukin   IQR = interquartile range   LDL = low-density lipoprotein   MI = myocardial infarction   NSTEMI = non–ST-segment elevation myocardial infarction   STEMI = ST-segment elevation myocardial infarction   UA = unstable angina