Ten estrogen-related polymorphisms and endometriosis: a study of multiple gene-gene interactions.
OBJECTIVE
Genetic as well as hormonal factors are known to influence the development and clinical course of endometriosis. We aimed to investigate the association among 10 single nucleotide polymorphisms (SNPs) involved in the estrogen metabolism and endometriosis and to develop a multiple genetic model.


METHODS
In a case-control study, we investigated the genotype frequencies of 10 estrogen metabolizing SNPs in 32 patients with endometriosis and 790 healthy controls using sequencing-on-chip-technology with solid-phase polymerase chain reaction on oligonucleotide microarrays: catechol-O-methyltransferase, Val158Met G->A, 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17), vlV A->C, cytochrome P450 (CYP), 17 A2 allele T->C, CYP1A1 MspI RFLP T->C, CYP1A1 Ile462Val A->G, CYP19 Arg264Cys C->T, CYP19 C1558T C->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser, and estrogen receptor alpha IVS1 -401>C. Associations and 2-way interaction models between SNPs were calculated by stepwise logistic regression models.


RESULTS
In a univariate model, HSD17 vlV A->C was associated with a significantly increased risk of endometriosis (P = .004; odds ratio 3.9, 95% confidence interval 1.6-9.8). When all 2-way interactions of investigated SNPs were ascertained, no significant interactions among SNPs were observed. In a multivariate model, HSD17 vlV A->C was also significantly associated with endometriosis (P = .002).


CONCLUSIONS
We present data on multiple SNPs in patients with endometriosis indicating an association between HSD17 gene variation and the disease. Although not able to demonstrate interaction models of SNPs, we provide evidence of HSD17 vlV A->C as a low penetrance genetic marker of endometriosis.


METHODS
II-2.
Huber
Ambros
A
Department of Obstetrics and Gynecology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Keck
Christoph C
CC
Hefler
Lukas A
LA
Schneeberger
Christian
C
Huber
Johannes C
JC
Bentz
Eva-Katrin
EK
Tempfer
Clemens B
CB
D000328:Adult; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics
D047628:Estrogen Receptor alpha; D003577:Cytochrome P-450 Enzyme System; D004960:Estradiol Dehydrogenases; D002394:Catechol O-Methyltransferase