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


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.
Mäkelä
R
R
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital, Finland. riikka.makela@uta.fi
Dastidar
P
P
Jokela
H
H
Jaakkola
O
O
Saarela
M
M
Punnonen
R
R
Lehtimäki
T
T
D000368:Aged; D001053:Apolipoproteins / Q000097:blood; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D008875:Middle Aged; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017698:Postmenopause / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
D001053:Apolipoproteins; D001323:Autoantibodies; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D009195:Peroxidase