ASSOCIATION OF DOPAMINE D-2 RECEPTOR GENE HAPLOTYPES WITH ANOVULATIONAND FECUNDITY IN FEMALE HISPANICS

Dopamine is an important neurotransmitter in the hypothalamic control of gonadotrophin secretion. Neuron response is mediated through one of five different dopamine receptors. We explored the association of D-2 receptor gene polymorphisms with disorders of ovulation. We utilized a multiplex allele specific polymerase chain reaction (PCR) to detect two bi-allelic polymorphisms (four potential haplotypes) in intron 5 a nd exon 6 of the D-2 receptor gene. A second PCR/restriction endonucle ase digest was utilized to verify this. Using these assays, 185 female Hispanics (51% with known ovulatory dysfunction and 49% with normal f unction) were haplotyped. One allele (3) was not present in the popula tion and there were no significant differences in remaining allele dis tribution between ovulatory and anovulatory patients. However, signifi cant associations were noted between alleles and gonadotrophins and fe cundity. The 4 allele had a different reproductive profile compared to the 2 allele. The 4 allele was associated with significantly higher c oncentrations of luteinizing hormone (LH) (means +/- SE) (19.2 +/- 2.2 versus 12.3 +/- 1.3 mIU/ml, P < 0.02) and follicle stimulating hormon e (FSH) (13.2 +/- 2.0 versus 10.0 +/- 0.6 mIU/ml, P < 0.05), significa ntly lower concentrations of prolactin (7.9 +/- 0.8 versus 14.9 +/- 3. 5 ng/ml, P < 0.02) and higher parity (1.4 +/- 0.12 versus 0.92 +/- 0.1 3) and lower miscarriage rates (0.89 +/- 0.1 versus 1.33 +/- 0.24, P < 0.04). We conclude that D-2 receptor alleles may be associated with r eproductive success through altered gonadotrophin secretion and that t his effect may be independent of ovulatory function.