Association between plasma levels of the soluble CD14 receptor of lipopolysaccharide and the C(-260)→T polymorphism in the promoter of the CD14 gene and coronary artery disease: investigations in a large case-control study

Abstract

Objectives: We sought to investigate the association of CD14 genotype a nd plasma levels of soluble (s)CD14 with risk of stable CAD, chronic infections and sensitive markers of systemic inflammation. Background: It has been suggested that genetic variation of the CD14 receptor with increased CD14 gene expression might play a role in atherogenesis. A mechanistic link would consist in its contribution to the inflammatory response seen in this disease. Methods: We measured levels of sCD14 (µg/ml; ELISA) in 312 patients with angiographically proven CAD and stable angina pectoris, and in 477 age- and sex-matched healthy blood donors. CD14 genotype was determined by polymerase chain reaction. In addition, seropositivity to Chlamydia pneumoniae (CP), and Helicobacter pylori (Hp), a complete lipid profile, and various sensitive systemic markers of inflammation were measured. Results: CD14 C(-260) →T genotype was not independently associated with increased risk of CAD after multivariable adjustments (Odds Ratio, OR 1.34; 95% confidence interval, CI, 0.84-2.16). However, sCD14 plasma levels were higher in subjects with TT genotype compared to those with CT or CC genotype (p=0.005). Plasma levels were not different between cases and controls (4.2 ± 1.3 µg/ml versus 4.3 ± 1.3 µg/ml, NS). In multivariable logistic regression, the OR for the presence of CAD was 1.11 (95% CI, 0.65-1.91), if the top quintile of the sCD14 distribution was compared to the bottom quintile. There was no consistent association between seropositivity to either CP or Hp or both and sCD14 levels, and between sCD14 levels or CD14 genotype and the various markers of inflammation. Conclusions: These results do not confirm an independent relationship between CD14 genotypes or plasma levels of sCD14 and risk of stable CAD in this population.