A common polymorphism in the CYP3A7 gene is associated with a nearly 50% reduction in serum dehydroepiandrosterone sulfate levels.
BACKGROUND
CYP3A7, expressed in the human fetal liver and normally silenced after birth, plays a major role in the 16alpha-hydroxylation of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and estrone. Due to a replacement of part of the CYP3A7 promoter with a sequence identical with the same region in the CYP3A4 promoter (referred to as CYP3A7*1C), some individuals still express a variant of the CYP3A7 gene later in life.


OBJECTIVE
The objective of this study was to examine the effect of the CYP3A7*1C polymorphism on serum steroid hormone levels.


METHODS
Two population-based cohort studies were performed. Study group 1 consisted of 208 subjects randomly selected from the Rotterdam Study, and study group 2 consisted of 345 elderly independently living men.


METHODS
Serum DHEA(S), androstenedione, estradiol, estrone, and testosterone levels were the main outcome measures.


RESULTS
In study groups 1 and 2, heterozygous CYP3A7*1C carriers had almost 50% lower DHEAS levels compared with homozygous carriers of the reference allele [study group 1, 1.74 +/- 0.25 vs. 3.33 +/- 0.15 micromol/liter (P = 0.02); study group 2, 2.09 +/- 0.08 vs. 1.08 +/- 0.12 micromol/liter (P < 0.001)]. No differences in circulating DHEA, androstenedione, estradiol, or testosterone levels were found. However, in study group 2, serum estrone levels were lower in heterozygous CYP3A7*1C carriers compared with homozygous carriers of the reference allele (0.11 +/- 0.002 vs. 0.08 +/- 0.006 nmol/liter; P < 0.001).


CONCLUSIONS
The CYP3A7*1C polymorphism causes the persistence of enzymatic activity of CYP3A7 during adult life, resulting in lower circulating DHEAS and estrone levels.
Department of Internal Medicine, Room Ee585, Erasmus Medical Center, Dr. Molewaterplein 40, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Pauline
P
Smit
Ron H N
RH
van Schaik
Marloes
M
van der Werf
Annewieke W
AW
van den Beld
Jan W
JW
Koper
Jan
J
Lindemans
Huibert A P
HA
Pols
Albert O
AO
Brinkmann
Frank H
FH
de Jong
Steven W J
SW
Lamberts
D000368:Aged; D000369:Aged, 80 and over; D000735:Androstenedione / Q000097:blood; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015331:Cohort Studies; D051544:Cytochrome P-450 CYP3A; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013739:Testosterone / Q000097:blood
D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D001189:Aryl Hydrocarbon Hydroxylases; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A