Endocrine Abstracts

Background: Recent studies have suggested an important role of advanced glycosylation end products receptor (RAGE) in the development of atherosclerosis. However, investigation of the relationship between RAGE polymorphisms (−429T/C, −374T/A) and coronary heart disease (CHD) has shown contradictory results. Furthermore, hyperandrogenemia in women postmenopause has been associated with an adverse CHD risk profile.

Aim of the study: To investigate any possible relationship between RAGE polymorphisms with CHD and the association of RAGE polymorphisms with cardiovascular risk factors in postmenopausal women.

Methods: Ninety-six menopausal women (28 diabetics – 68 non-diabetics, mean age: 68, 34 years) who underwent coronary angiography were genotyped for the −429T/C and −374T/A variants of RAGE. In this group, androgen and estrogen levels, lipid parameters, glucose, HbA1c and insulin were determined and free androgen index was calculated.

Results: There was no significant difference in RAGE polymorphism frequencies between women with CHD confirmed in coronary angiography and those without CHD, although a cardioprotective trend was disclosed for 374AA polymorphism. Regarding hormonal/metabolic profile, women with homozygosity for the −429 allele (TT) had significantly lower levels of HDL (43,7±17.16 vs 52,95±14.47, P=0.036) and SHBG (42.73±18.17 vs 52.55±20.71, P=0.038) compared to heterozygotic subjects (TC) and significantly higher levels of triglycerides (151.75±50.65 vs 125.89±36.64, P=0.042), FAI (1.85±1.43 vs 1.17±0.84, P=0.042) and androstenedione (1.61±1.01 vs 1.22±0.58, P=0.031). Women with homozygosity for the −374 allele (AA) had significantly lower LDL levels (83.8±21.96 vs 105±42.97, P=0.046) compared to heterozygotic (AT) subjects.

Conclusion: Our data did not demonstrate an association between polymorphisms of the RAGE gene and CHD in menopausal women. However, homozygosity for the −429 allele (TT) of RAGE is associated with an adverse lipid profile and hyperandrogenemia and its role as a predisposing factor of atherosclerosis needs further evaluation.