Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women.
BACKGROUND
In mice, anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment and decreases FSH sensitivity. Little is known about the role of AMH in human ovarian physiology. We hypothesize that in women AMH has a similar role in ovarian function as in mice and investigated this using a genetic approach.


METHODS
The association of the AMH Ile(49)Ser and the AMH type II receptor (AMHR2) -482 A > G polymorphisms with menstrual cycle characteristics was studied in a Dutch (n = 32) and a German (n = 21) cohort of normo-ovulatory women.


RESULTS
Carriers of the AMH Ser(49) allele had higher serum estradiol (E(2)) levels on menstrual cycle day 3 when compared with non-carriers in the Dutch cohort (P = 0.012) and in the combined Dutch and German cohort (P = 0.03). Carriers of the AMHR2 -482G allele also had higher follicular phase E(2) levels when compared with non-carriers in the Dutch cohort (P = 0.028), the German cohort (P = 0.048) and hence also the combined cohort (P = 0.012). Women carrying both AMH Ser(49) and AMHR2 -482G alleles had highest E(2) levels (P = 0.001). For both polymorphisms no association with serum AMH or FSH levels was observed.


CONCLUSIONS
Polymorphisms in the AMH and AMHR2 genes are associated with follicular phase E(2) levels, suggesting a role for AMH in the regulation of FSH sensitivity in the human ovary.
Kevenaar
Marlies E
ME
Department of Internal Medicine, Erasmus MC, 3000 CA Rotterdam, The Netherlands. m.kevenaar@erasmusmc.nl
Themmen
Axel P N
AP
Laven
Joop S E
JS
Sonntag
Barbara
B
Fong
Sharon Lie
SL
Uitterlinden
André G
AG
de Jong
Frank H
FH
Pols
Huibert A P
HA
Simoni
Manuela
M
Visser
Jenny A
JA
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D054304:Anti-Mullerian Hormone; D004958:Estradiol / Q000097:blood*; D005260:Female; D005498:Follicular Phase / Q000097:blood* / Q000235:genetics*; D005787:Gene Frequency; D006023:Glycoproteins / Q000097:blood / Q000235:genetics*; D006801:Humans; D007532:Isoleucine / Q000737:chemistry / Q000235:genetics; D011110:Polymorphism, Genetic; D018000:Receptors, Peptide / Q000097:blood / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta; D012694:Serine / Q000737:chemistry / Q000235:genetics; D013735:Testicular Hormones / Q000097:blood / Q000235:genetics*
D006023:Glycoproteins; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D013735:Testicular Hormones; C084621:anti-Mullerian hormone receptor; D007532:Isoleucine; D012694:Serine; D004958:Estradiol; D054304:Anti-Mullerian Hormone