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 (D3) receptor genotypes are associated with anovulation and response to ovulation induction with clomiphene citrate.


METHODS
Clinical and laboratory characteristics of anovulatory patients and ovulatory controls were compared with findings at the DNA level.


METHODS
An outpatient clinic at an university medical center.


METHODS
One hundred eighty human Hispanic female volunteers (130 of these with documented ovulatory status) were studied.


METHODS
Genomic DNAs were extracted from each patient. Polymerase chain reaction with subsequent restriction digest was performed to analyze the D3 receptor allele status (two possible alleles).


METHODS
Menstrual history, serum T, and midluteal serum Ps from spontaneous and clomiphene cycles were correlated with D3 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 (> or = 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.
Legro
R S
RS
University of Southern California, Los Angeles, Duarte.
Muhleman
D R
DR
Comings
D E
DE
Lobo
R A
RA
Kovacs
B W
BW
D000483:Alleles; D000858:Anovulation / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics*; D001483:Base Sequence; D002908:Chronic Disease; D002996:Clomiphene / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications* / Q000208:ethnology; D008597:Menstrual Cycle; D008599:Menstruation Disturbances / Q000150:complications; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010062:Ovulation Induction; D011374:Progesterone / Q000097:blood; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013739:Testosterone / Q000097:blood
C493593:DRD3 protein, human; D015335:Molecular Probes; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D002996:Clomiphene; D013739:Testosterone; D011374:Progesterone