A dopamine D3 receptor genotype is associated with hyperandrogenic chronic anovulation and resistant to ovulation induction with clomiphene citrate in female Hispanics

Objective To determine if dopamine (D 3 ) receptor genotypes are associated with anovulation and response to ovulation induction with clomiphene citrate. Design Clinical and laboratory characteristics of anovulatory patients and ovulatory controls were compared with findings at the DNA level. Setting An outpatient clinic at an university medical center. Patients One hundred eighty human Hispanic female volunteers (130 of these with documented ovulatory status) were studied. Interventions Genomic DNAs were extracted from each patient. Polymerase chain reaction with subsequent restriction digest was performed to analyze the D 3 receptor allele status (two possible alleles). Main Outcome Measures Menstrual history, serum T, and midluteal serum Ps from spontaneous and clomiphene cycles were correlated with D 3 receptor genotype. Results Hispanic females with the 22 genotype compared with the other genotypes ( 11 and 12 ) were more likely to have irregular menses, an elevated serum T (≥70 ng/dL [conversion factor to SI unit, 3.467]), and hyperandrogenic chronic anovulation. These patients tended to be resistant to ovulation induction requiring a significantly higher dose of clomiphene to achieve an ovulatory response ( 22 genotype [mean ± SEM] [140.0 ± 19.0 mg] versus 11 [77.1 ± 17.5 mg] or 12 [69.2 ± 13.1 mg]). This effect was independent of patient age, weight, or serum T level. Conclusions Hyperandrogenic chronic anovulation may have a genetic component. Genetic analysis may be useful in predicting resistance to ovulation induction with clomiphene.