title: Effect of long-term hormone replacement therapy on atherosclerosis progression in postmenopausal women relates to myeloperoxidase promoter polymorphism.
abstract: Myeloperoxidase (MPO) is an oxidative enzyme present in phagocytes and atherosclerotic lesions. The MPO gene has a promoter polymorphism -463G/A, which leads to high (GG) and low expression (AG, AA) genotypes. We investigated the effect of long-term hormone replacement therapy (HRT) on the progression of atherosclerosis in a 5-yr follow-up study of postmenopausal women with different MPO genotypes. Eighty-seven nonsmoking postmenopausal women, aged 45-71 yr, were divided into three groups based on the use of HRT. The HRT-EVP group (n = 25) used sequential estradiol valerate plus progestin, the HRT-EV group used estradiol valerate alone (n = 32), and the control group (n = 30) used no HRT. The atherosclerosis severity score (ASC) for abdominal aorta and carotid arteries was determined by ultrasonography, and the MPO genotype was analyzed. In subjects with the GG genotype, the progression of ASC was significantly faster in the control group than in the HRT group (genotype by time interaction, P = 0.042), whereas in A allele carriers there were no significant differences in ASC progression between control and HRT. The effects of HRT on atherosclerosis progression in subjects with the GG genotype seem to be especially beneficial compared with controls with the same genotype but without HRT. These results may help us understand in greater detail the benefit and possible risk of HRT in atherosclerotic diseases.
authors.affiliation: Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Center for Laboratory Medicine, University Hospital of Tampere, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Mäkelä
authors.forename: Prasun
authors.initials: P
authors.lastname: Dastidar
authors.forename: Hannu
authors.initials: H
authors.lastname: Jokela
authors.forename: Marika
authors.initials: M
authors.lastname: Saarela
authors.forename: Reijo
authors.initials: R
authors.lastname: Punnonen
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000368:Aged; D000483:Alleles; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D015914:Estrogen Replacement Therapy; D005260:Female; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D014463:Ultrasonography
chemical_list: D009195:Peroxidase