Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy.
Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, are associated with the risk of atherothrombosis. Plasma levels of these markers of inflammation are affected by hormone replacement therapy (HRT) and modulated by smoking. We studied whether genetic variation in the estrogen receptor- 1 (ESR1), CRP and fibrinogen-beta genes influences the plasma levels of inflammation markers after HRT. Plasma CRP and fibrinogen were measured after five years follow-up in healthy postmenopausal women (per-protocol group) who were randomised to hormone therapy (n=187) or no treatment (n=249). The effect of HRT, smoking and genetic variations in ESR1 (PvuII and XbaI), CRP (1444C/T) and fibrinogen-beta (FGB, -455G/A) were determined. The plasma concentration of CRP was higher in the HRT group than in the control group (2.03 mg/l and 1.41 mg/l, respectively; p < 0.001), while the concentration of fibrinogen was lower in the HRT group than in the control group (3.02 g/l and 3.20 g/l, respectively; p < 0.001), indicating that it is unlikely that inflammation is the common underlying pathway. There was a significant interaction between smoking and HRT on the fibrinogen (p=0.02), but not on the CRP concentration (n.s.). Genetic polymorphisms in ESR1, CRP and fibrinogen were not associated with an effect of HRT on the CRP and fibrinogen plasma levels, and no significant interaction with smoking was observed. In conclusion, higher plasma levels of CRP and lower plasma levels of fibrinogen were observed in women using HRT; however, genetic polymorphisms in ESR1, CRP and FGB were not associated with these effects of HRT.
de Maat
Moniek P M
MP
Department for Thrombosis research, Institute of Public Health, University of Southern Denmark, Denmark. m.demaat@erasmusmc.nl
Madsen
Jonna Skov
JS
Langdahl
Bente
B
Bladbjerg
Else Marie
EM
Tofteng
Charlotte Landbo
CL
Abrahamsen
Bo
B
Rejnmark
Lars
L
Brixen
Kim
K
Christensen
Kaare
K
Jespersen
Jørgen
J
Kristensen
Søren Risom
SR
D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D003718:Denmark; D047628:Estrogen Receptor alpha / Q000235:genetics*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007044:Hysterectomy; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000097:blood / Q000235:genetics; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D047628:Estrogen Receptor alpha; D005340:Fibrinogen; D002097:C-Reactive Protein