PPBP gene as a biomarker for coronary heart disease risk in postmenopausal Thai women

Estrogen is an important ovarian hormone with anti-atherogenic and cardioprotective effects. Postmenopausal women have lower estrogen levels, associated with significantly higher risks of coronary heart disease (CHD) and CHD-related death. Effective biomarkers for the diagnosis, prediction, and treatment of CHD are needed to address this problem and thus reduce the mortality due to CHD in postmenopausal women. We recently reported that the PPBP and DEFA1/DEFA3 genes may be feasible synergistic biomarkers for CHD risk in Thai men with hyperlipidemia. The PPBP gene encodes pro-platelet basic protein (PPBP) from activated platelets, and DEFA1/DEFA3 encodes human neutrophil peptides (HNP) 1-3, mainly produced by activated neutrophils. Both platelets and neutrophils are involved in chronic inflammation during the development of atherogenesis and CHD. This study investigated the potential roles of PPBP and DEFA1/DEFA3 and their proteins as biomarkers for CHD risk in postmenopausal Thai women.

The results indicate that gene and protein expression levels of PPBP, but not DEFA1/DEFA3, and HNP-1-3, may be feasible biomarkers for assessing CHD risk in postmenopausal Thai women with hyperlipidemia.

This cross-sectional study enrolled 90 postmenopausal Thai women, including 12 healthy controls (N), 18 patients with hyperlipidemia (H), and 21 patients diagnosed with CHD. The remaining 39 women were receiving cholesterol-lowering drugs for hyperlipidemia (HD) were excluded from the study. All CHD patients underwent coronary bypass grafting or coronary angioplasty. PPBP and DEFA1/DEFA3 mRNA expression levels in peripheral blood mononuclear cells isolated from heparinized blood were determined by quantitative reverse-transcription polymerase chain reaction. Levels of PPBP and HNP-1-3 proteins in corresponding plasma samples were assessed by enzyme-linked immunosorbent assay. Differences in parameters were compared among groups and correlations between parameters and clinical manifestations were analyzed.

PPBP mRNA and protein levels were significantly increased in the CHD group compared with the N and H groups. In contrast, DEFA1/DEFA3 mRNA and HNP-1-3 protein levels did not differ significantly among the groups. None of the levels were associated with any of the clinical parameters analyzed in this study.