The effects of osteoprotegerin (OPG) gene polymorphism in patients with ischaemic heart disease on the morphology of coronary arteries and bone mineral density

Abstract

Background: The incidence of coronary artery disease (CAD) and osteoporosis increases with age, especially in the elderly. Many studies have shown that vessel calcification is associated with low bone mineral density (BMD) and an increased risk of bone fractures. Experimental studies have shown that osteoprotegerin (OPG) gene knockout mice have aortic calcification and osteoporosis at the same time.

Aim: To assess the frequency of OPG gene polymorphisms in patients with CAD and to analyse the relationship between the severity of CAD and BMD.

Methods: The study group comprised 31 postmenopausal women (mean age 65.6, range 39-82 years) undergoing elective coronary angiography for CAD symptoms. The BMD was measured at the hip by dual X-ray absorptiometry (DEXA). Clinical data were collected using a questionnaire developed by the authors which addressed CAD risk factors, treatment, previous diagnosis of osteoporosis and the risk factors of osteoporosis. The control group consisted of 30 postmenopausal women attending the osteoporosis clinic without the history of CAD (mean age 70.5, range 56-84 years). Written informed consent was obtained from all the patients. Genotyping of two polymorphisms 209, 245 in the promoter region and 1181 in the exon of the OPG gene was performed in both groups.

Results: Coronary angiography in study group revealed normal coronary arteries in 35% (n = 11) of the women. The analysis of 209 C/T polymorphism showed no presence of TT homozygotes in either group. Also, no significant differences between the 209 C/T polymorphic variants, BMD and progression of atherosclerosis in coronary arteries were found. In both groups no CC homozygous variants for 245 A/C were revealed. However, a statistically significant relationship between 245 A/C polymorphism and BMD was shown. The AC carriers had osteoporosis more frequently (57%) than AA carriers (12%) of the OPG gene (p = 0.0382). There were no significant differences in the OPG gene 245 A/C polymorphisms and CAD progression. Homozygotes for CC 1181 were shown to have normal coronary arteries more frequently (60%) than heterozygotes for CG 1181 (29%; p = 0.0023). We failed to show significant differences between 1181 C/G polymorphism and BMD in both groups.

Conclusions: 1. This study revealed a significant association between homozygotes for AA 245 and normal BMD in study group. 2. The analysis of 209 C/T and 245 C/T C polymorphisms has shown no presence of homozygotes for TT 209 OPG or CC 245 OPG in both groups. 3. Carriers of the homozygous CC 1181 OPG gene were shown to have normal coronary arteries more frequently when compared to heterozygotes for CG or homozygotes for GG.