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.
Smit
Pauline
P
Department of Internal Medicine, Room Ee585, Erasmus Medical Center, Dr. Molewaterplein 40, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
van Schaik
Ron H N
RH
van der Werf
Marloes
M
van den Beld
Annewieke W
AW
Koper
Jan W
JW
Lindemans
Jan
J
Pols
Huibert A P
HA
Brinkmann
Albert O
AO
de Jong
Frank H
FH
Lamberts
Steven W J
SW
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