Relation of myeloperoxidase promoter polymorphism and long‐term hormone replacement therapy to oxidized low‐density lipoprotein autoantibodies in postmenopausal women

Abstract

Objective. The myeloperoxidase enzyme (MPO) is a potent precursor of low‐density lipoprotein (LDL) oxidation in atherosclerotic lesions. The MPO gene has a promoter polymorphism, 463G/A, which leads to high (GG) and low‐expression (AG, AA) genotypes. Hormone replacement therapy (HRT) is known to affect MPO activity and LDL oxidation. The purpose of this study was to test whether the effect of HRT on the levels of oxLDL‐ab varies according to MPO genotype. Material and methods. Eighty‐seven postmenopausal women aged 45–71 years were divided into three groups based on the use of HRT. The HRT‐EVP group (n = 25) used sequential estradiol valerate (EV) plus progestin, the HRT‐EV group (n = 32) used EV alone, and the control group (n = 30) no HRT. MPO genotypes were determined by polymerase chain reaction (PCR) and oxLDL‐ab by ELISA. Results. We found a significant HRT group by MPO genotype interaction (p = 0.021) in plasma oxLDL‐ab levels. In subjects with the GG genotype, the oxLDL‐ab titer increased in the order of 2.13 in controls, 2.53 in the EV group and 3.21 in the EVP group (ANOVA for trend p = 0.006). Conclusions. The effects of HRT on LDL oxidation can vary according to MPO genotype and the concurrent progestin therapy with EV may counteract the more neutral effect of EV on LDL oxidation in subjects with the MPO high‐expression genotype.

• Atherosclerosis
• hormone replacement therapy
• LDL oxidation
• myeloperoxidase

Acknowledgements

This study was supported by the Finnish Foundation of Cardiovascular Research (Helsinki, Finland), the Elli and Elvi Oksanen Fund of the Pirkanmaa Fund under the auspices of the Finnish Cultural Foundation, the Emil Aaltonen Foundation, the Juho Vainio Foundation, the Research Foundation of Orion Corporation, the Medical Research Fund of Tampere University Hospital and the Finnish Medical Society Duodecim (Tampere, Finland). We thank Nina Peltonen for skillful technical assistance.