Genetic polymorphisms associated with steroids metabolism and insulin action in polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is an endocrinopathy associated with infertility, diabetes and cardiovascular events. This study aimed to correlate polymorphisms of genes involved in the biosynthesis and metabolism of steroids and insulin action (CYP17A1, CYP19A1, AR, ESR1, ESR2, INSR, IGF2 and PAI1) with clinical and biochemical parameters of PCOS. DNA was extracted from peripheral blood samples obtained from 117 PCOS and 105 healthy women. The PAI1 insertion/deletion (-675 ins/delG) polymorphism (rs1799768) was genotyped by PCR-SSCP. CYP19A1 [TTTA]_n, AR [CAG]_n, ESR1 [TA]_n, and ESR2 [CA]_n genes were evaluated by PCR-based GeneScan analysis, while CYP17A1 5′UTR (rs743572), INSR 1058 CT (rs1799817), and IGF2 3′UTR GA (rs680) polymorphisms were evaluated by PCR-RFLP. The results showed a prevalence of PAI1 4G5G+4G4G genotypes in PCOS (p = 0.025). Younger PCOS women showed a predominance of CT+TT, GA+AA and 4G5G+4G4G genotypes of INSR, IGF2, and PAI1 (p = 0.0499, p = 0.0300, p = 0.0350, respectively). AR shorter alleles (≤ 20 repeats) were significantly associated with higher serum levels of total testosterone (TT, p = 0.0086). In conclusion, PAI1 polymorphism seems to be associated with the risk of PCOS development. Younger PCOS women had specific genotypes of INSR, IGF2 and PAI1 genes. AR shorter alleles can be associated with higher serum levels of TT in PCOS patients.

Keywords::

• Polycystic ovary syndrome
• androgen metabolism
• androgen receptor
• estrogen receptor
• insulin resistance
• infertility

Acknowledgements

The authors gratefully acknowledge Hélio Rubens de Carvalho Nunes and Sabrina Daniela da Silva for their assistance with the statistical analysis, and Sandra Aparecida Drigo for her assistance with the final revision of manuscript. This study was supported by Grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.