Polymorphisms in ESR1, ESR2 and HSD17B1 genes are associated with fertility status in endometriosis

Abstract

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.

Materials and 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.

Keywords:

• Aromatase
• endometriosis
• infertility
• oestrogen receptor
• polymorphism
• progesterone receptor
• 17β-hydroxysteroid dehydrogenase type 1

Acknowledgements

The authors acknowledge all the voluntary participants of the study. This study was supported by the European Union via European Regional Development Fund and the Centre of Excellence in Genomics, Estonian Biocentre and University of Tartu; the Estonian Science Foundation (grant nos. 6498 and 6585); the Estonian Ministry of Education and Science (core grant nos. 0180044s09, 0180142s08, and PBGMR07903); and by the Enterprise Estonia (grant no. EU30200).