Cytochrome gene polymorphisms, serum estrogens, and hot flushes in midlife women.
OBJECTIVE
The purpose of this study was to evaluate whether genetic polymorphisms in selected cytochrome P450 enzymes (CYPc17alpha, CYP1A1, and CYP1B1), estradiol (E2) levels, and estrone levels were associated with hot flushes.


METHODS
Women with hot flushes were those aged 45-54 years who reported ever experiencing hot flushes (n = 354). Women without hot flushes were those aged 45-54 years who reported never experiencing hot flushes (n = 258). Each participant completed a questionnaire and provided a blood sample for determination of genotypes, E2 levels, and estrone levels.


RESULTS
Carriers of the CYP1B1 (Val432Leu) polymorphism were more likely to report having any hot flushes (risk ratio [RR] 1.16, 95% confidence interval (CI) 0.98-1.37) and at least weekly hot flushes (RR 1.29, 95% CI 0.98-1.70) than women without the polymorphism, although these associations were of borderline statistical significance. In addition, carriers of the CYP1B1 polymorphism were likely to have a statistically significant 30% increased risk of reporting moderate to severe hot flushes (RR 1.30, 95% CI 1.02-1.67) and a statistically significant 27% increased risk of reporting hot flushes lasting a year or more (RR 1.27, 95% CI 1.00-1.61) compared with women without the polymorphism. There were no associations between CYP1A1 or CYPc17alpha polymorphisms and hot flushes. Low E2 and estrone levels were associated with hot flushes, but they did not alter the association between the CYP1B1 polymorphism and hot flushes.


CONCLUSIONS
These data suggest that a CYP1B1 polymorphism may be associated with severe and persistent hot flushes, independent of E2 and estrone levels.
Visvanathan
Kala
K
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21201, USA.
Gallicchio
Lisa
L
Schilling
Chrissy
C
Babus
Janice K
JK
Lewis
Lynn M
LM
Miller
Susan R
SR
Zacur
Howard
H
Flaws
Jodi A
JA
D015331:Cohort Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004967:Estrogens / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D019584:Hot Flashes / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000235:genetics; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
D004967:Estrogens; D005819:Genetic Markers; D019363:Cytochrome P-450 CYP1A1