Association between endometriosis and genetic polymorphisms of the estradiol-synthesizing enzyme genes HSD17B1 and CYP19.
BACKGROUND
Endometriosis, an estrogen-dependent disease, is believed to be influenced by multiple genetic and environmental factors. Here, we evaluated whether the risk and severity of endometriosis are associated with polymorphisms in estradiol-synthesizing enzyme genes: the Ser312Gly polymorphism in 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and the Arg264Cys polymorphism in cytochrome P450, subfamily XIX (CYP19).


METHODS
All participants underwent diagnostic laparoscopy, and the stage of endometriosis was determined according to the Revised American Fertility Society classification. Of the 138 women enrolled, 59 had no endometriosis, 21 had stage I, 10 had stage II, 23 had stage III and 25 had stage IV. SNPs were discriminated by allele-specific oligonucleotide hybridization.


RESULTS
Individuals having at least one A-allele (A/G or A/A genotype) of HSD17B1 showed a significantly increased risk of endometriosis (A/G genotype: adjusted OR, 3.06; 95%CI 1.21-7.74; A/A genotype: adjusted OR, 3.02; 95%CI 1.08-8.43). There was a significant trend associating A/G + A/A genotypes with severity of endometriosis (P for trend < 0.01). No statistically significant association was found for the CYP19 polymorphism.


CONCLUSIONS
Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis.
Tsuchiya
M
M
Department of Public Health, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Japan.
Nakao
H
H
Katoh
T
T
Sasaki
H
H
Hiroshima
M
M
Tanaka
T
T
Matsunaga
T
T
Hanaoka
T
T
Tsugane
S
S
Ikenoue
T
T
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004715:Endometriosis / Q000453:epidemiology / Q000235:genetics*; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012720:Severity of Illness Index
D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase