Polymorphisms in ESR1, ESR2 and HSD17B1 genes are associated with fertility status in endometriosis.
OBJECTIVE
To investigate whether polymorphisms in genes involved in biosynthesis and signalling of sex steroids influence susceptibility to endometriosis and to infertility associated with it.


METHODS
Patients with endometriosis (n = 150) and fertile controls (n = 199) were genotyped for polymorphisms in oestrogen receptor genes ESR1 (rs2234693 - T/C single nucleotide polymorphism (SNP), dinucleotide (TA)(n) repeat) and ESR2 (dinucleotide (CA)(n) repeat), progesterone receptor gene PGR (rs10895068 - G/A SNP, 306-bp Alu-insertion), 17β-hydroxysteroid dehydrogenase type 1 gene HSD17B1 (rs605059 - A/G SNP), and aromatase gene CYP19A1 (rs10046 - C/T SNP, (TTTA)(n) tetranucleotide repeat, 3-bp TCT insertion/deletion polymorphism).


RESULTS
The HSD17B1 A/G SNP A allele increased overall endometriosis risk and the risk of stage I-II disease, while ESR1 longer (TA)(n) repeats only correlated with susceptibility to stage I-II endometriosis. When considering patients' fertility status, HSD17B1 A/G SNP A allele and ESR1 longer (TA)(n) repeats were associated with endometriosis accompanied by infertility, while ESR2 shorter (CA)(n) repeats were linked with endometriosis without infertility. Other polymorphisms were distributed similarly among patients and controls.


CONCLUSIONS
Genetic variants in ESR1, ESR2, and HSD17B1 genes could modify susceptibility to endometriosis and might influence the fertility status in endometriosis patients.
Lamp
Merit
M
Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia. merit.lamp@ut.ee
Peters
Maire
M
Reinmaa
Eva
E
Haller-Kikkatalo
Kadri
K
Kaart
Tanel
T
Kadastik
Ulle
U
Karro
Helle
H
Metspalu
Andres
A
Salumets
Andres
A
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004715:Endometriosis / Q000150:complications / Q000235:genetics*; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005298:Fertility / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006304:Health Status; D006801:Humans; D007247:Infertility, Female / Q000150:complications / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology; D014591:Uterine Diseases / Q000150:complications / Q000235:genetics*; D055815:Young Adult
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human