ABSTRACT
AIMS: To correlate differences in estradiol levels in serum and follicular fluid with genetic variants and to determine if they play a role in the results following assisted reproductive technology (ART). PATIENTS AND METHODS: A cross-sectional study was developed at the Ideia Fértil Institute of Reproductive Health. Two hundred two female patients were selected and underwent controlled ovarian hyperstimulation cycles. Patients for this study were chosen based on their male partners' infertility. Genotypes of selected variants of CYP19A1, CYP17A1, HSD17, and COMT were compared to the estradiol measurements from follicular fluid and serum, as well as to the number and maturation status of the oocytes retrieved. RESULTS: Patients with the variant homozygous genotype AA of CYP19A1 (rs10046) showed increased serum concentrations of estradiol when compared to patients with other genotypes (p = 0.005). The same polymorphism effect was not observed in follicular fluid. This CYP19A1 variant did not affect the number of oocytes recovered nor their maturation level. CONCLUSION: The CYP19A1 variant is associated with an estradiol imbalance in serum. Other pathways, however, may contribute to the formation of the final estradiol metabolite in follicular fluid as well as its impact on the oocyte maturation.
Subject(s)
Aromatase/genetics , Estradiol/genetics , Adult , Alleles , Aromatase/metabolism , Catechol O-Methyltransferase/genetics , Catechol O-Methyltransferase/metabolism , Cross-Sectional Studies , Estradiol/analysis , Estradiol/blood , Estradiol Dehydrogenases/genetics , Estradiol Dehydrogenases/metabolism , Female , Fertilization in Vitro/methods , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/metabolism , Follicular Fluid , Gene Frequency/genetics , Genotype , Humans , Luteinizing Hormone/metabolism , Oocyte Retrieval/methods , Ovulation Induction/methods , Steroid 17-alpha-Hydroxylase/genetics , Steroid 17-alpha-Hydroxylase/metabolism , Young AdultABSTRACT
We tested the hypothesis that polymorphisms in cytochrome P450c17alpha (CYP17), aromatase (CYP19), 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD1) and sex hormone-binding globulin (SHBG) genes may modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based, case-control studies in Nagano, Japan and Sao Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians, and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. Four single nucleotide polymorphisms (SNPs) in CYP17 (rs743572), CYP19 (rs10046), 17beta-HSD1 (rs605059), and SHBG (rs6259) genes were genotyped. We found no association between the 4 SNPs and breast cancer risk. In combination analyses of isoflavone intake and SNPs, an inverse association between intake and risk was limited to women with at least one A allele of the rs605059 polymorphism for all 3 populations, albeit without statistical significance. For the rs6259 polymorphism, the inverse association was limited to postmenopausal Japanese with the GG genotype (odds ratio [OR] for highest vs. lowest tertile = 0.50, 95% confidence interval [CI] = 0.29-0.87; P for trend < 0.01), and to non-Japanese Brazilians with at least one A allele (OR for consumers vs. nonconsumer = 0.21, 95% CI = 0.06-0.77). We found no remarkable difference for the rs743572 and rs10046 polymorphisms. Our findings suggest that polymorphisms in the 17beta-HSD1 and SHBG genes may modify the association between isoflavone intake and breast cancer risk.