Effect of NFE2L2 genetic polymorphism on the association between oral estrogen therapy and the risk of venous thromboembolism in postmenopausal women.
Oral, but not transdermal, estrogen therapy increases the risk of venous thromboembolism (VTE) in women who are past menopause. Data from the Estrogen and Thromboembolism Risk (ESTHER) study were used to investigate the effects of the genetic polymorphism of NFE2L2 rs6721961, which may impair Nrf2-dependent hepatic conjugation of estrogen metabolites. As compared with nonusers, the odds ratio (OR) for VTE in current users of oral estrogens was 2.5 (95% confidence interval (CI): 1.3-4.8) in patients with wild-type NFE2L2 and 17.9 (95% CI: 3.7-85.7) in those with the polymorphism (interaction, P = 0.01).
Laboratoire de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Hôpital Bicêtre, AP-HP, Univ Paris-Sud, Le Kremlin Bicêtre, France. jerome.bouligand@bct.aphp.fr
J
J
Bouligand
O
O
Cabaret
M
M
Canonico
C
C
Verstuyft
L
L
Dubert
L
L
Becquemont
A
A
Guiochon-Mantel
P Y
PY
Scarabin
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D016022:Case-Control Studies; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000235:genetics*; D020246:Venous Thrombosis / Q000453:epidemiology / Q000235:genetics
D004967:Estrogens; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D004958:Estradiol