Alternatively, they might constitute a marker for a mutated gene nearby. We assessed the prevalence of seven SNPs in six genes involved in steroid hormone biosynthesis and metabolism, i.e. estrogen receptor alpha (ESRI, PvuII and Xba1) and beta (ESRII, 3 0 UTR+38), aromatase (CYP19, 1531A>G, 17-hydroxylase/17,20-lyase (CYP17, ex1-34T>C), hexose-6-phosphate dehydrogenase (H6PD, Arg453Gln) and 11b-hydroxysteroid dehydrogenase (HSD11B1, 83557insA). Materials and methods: To establish association
... these SNPs with WHO II (World Health Organization class II) anovulatory infertility phenotype, we conducted a cross-sectional study in 643 normogonadotrophic anovulatory infertile women of whom 576 were diagnosed with PCOS (revised Rotterdam criteria). All participants underwent a standardized evaluation that included cycle history, body mass index (BMI) measurement, and transvaginal ultrasonographic assessment of the number of follicles and ovarian volume. Fasting blood samples were obtained for endocrine evaluation. DNA was isolated from peripheral blood samples and genotyping was done using TaqMan PCR assays. We compared the genotype distribution to a random sample of 3632 healthy women (the Rotterdam Study). Main outcome parameters were gonadotropin levels (follicle stimulating hormone and luteinizing hormone), estrogen level, androstenedione (AD), testosterone (T), dehydroepiandrosterone and dehydroepiandrosterone sulfate. Results: No deviations from Hardy-Weinberg equilibrium were found for all SNPs tested. The G allele of the CYP19 A1531G SNP was found more often in WHO II anovulatory women compared to the control group (57% vs. 49%, x 2 p<0.001). In comparison with the A/A genotype, homozygosity for the G allele was associated with a 10% and 14% increase in median AD and T levels, respectively. Kruskall-Wallis test for the differences in androgen levels between the three groups (genotypes A/A, A/G and G/G) was significant for both AD (p¼0.04) and T (p¼0.01). Conclusions: The G allele of the CYP19 A1531G polymorphism was more prevalent among WHO II anovulatory infertile women compared to a random sample of healthy women. Furthermore, the G/G genotype was associated with increased levels of androstenedione and testosterone. Possibly, a less active state of the enzyme aromatase could (partly) explain hyperandrogenism in WHO II anovulation and PCOS. The association of this SNP with WHO II anovulatory infertility and PCOS warrants further investigation into the specific role of the enzyme aromatase in this disease.