Genetics: Association of dopamine D2 receptor gene haplotypes with anovulation and fecundity in female hispanics

Richard Legro, George W. Dietz, David E. Comings, Rogerio A. Lobo, Bruce W. Kovacs

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Dopamine is an important neurotransmitter in the hypo-thalamic control of gonadotrophin secretion. Neuron response is mediated through one of five different dopamine receptors. We explored the association of D2 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 and exon 6 of the D2 receptor gene. A second PCR/restriction endonuclease digest was utilized to verify this. Using these assays, 185 female Hispanics (51% with known ovulatory dysfunction and 49% with normal function) were haplotyped. One allele (3) was not present in the population and there were no significant differences in remaining allele distribution between ovulatory and anovulatory patients. However, significant associations were noted between alleles and gonadotrophins and fecundity. The 4 allele had a different reproductive profile compared to the 2 allele. The 4 allele was associated with significantly higher concentrations of lutein-izing hormone (LH) (means ± SE) (19.2 ± 2.2 versus 12.3 ± 1.3 mIU/ml, P < 0.02) and follicle stimulating hormone (FSH) (13.2 ± 2.0 versus 10.0 ± 0.6 mIU/ml, P < 0.05), significantly 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 ± 0.13) and lower miscarriage rates (0.89 ± 0.1 versus 1.33 ± 0.24, P < 0.04). We conclude that D2 receptor alleles may be associated with reproductive success through altered gonadotrophin secretion and that this effect may be independent of ovulatory function.

Original languageEnglish (US)
Pages (from-to)1271-1275
Number of pages5
JournalHuman Reproduction
Volume9
Issue number7
DOIs
StatePublished - Jan 1 1994

Fingerprint

Anovulation
Dopamine D2 Receptors
Hispanic Americans
Haplotypes
Fertility
Alleles
Genes
Gonadotropins
Lutein
Polymerase Chain Reaction
DNA Restriction Enzymes
Dopamine Receptors
Follicle Stimulating Hormone
Spontaneous Abortion
Ovulation
Parity
Prolactin
Introns
Neurotransmitter Agents
Exons

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Legro, Richard ; Dietz, George W. ; Comings, David E. ; Lobo, Rogerio A. ; Kovacs, Bruce W. / Genetics : Association of dopamine D2 receptor gene haplotypes with anovulation and fecundity in female hispanics. In: Human Reproduction. 1994 ; Vol. 9, No. 7. pp. 1271-1275.
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abstract = "Dopamine is an important neurotransmitter in the hypo-thalamic control of gonadotrophin secretion. Neuron response is mediated through one of five different dopamine receptors. We explored the association of D2 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 and exon 6 of the D2 receptor gene. A second PCR/restriction endonuclease digest was utilized to verify this. Using these assays, 185 female Hispanics (51{\%} with known ovulatory dysfunction and 49{\%} with normal function) were haplotyped. One allele (3) was not present in the population and there were no significant differences in remaining allele distribution between ovulatory and anovulatory patients. However, significant associations were noted between alleles and gonadotrophins and fecundity. The 4 allele had a different reproductive profile compared to the 2 allele. The 4 allele was associated with significantly higher concentrations of lutein-izing hormone (LH) (means ± SE) (19.2 ± 2.2 versus 12.3 ± 1.3 mIU/ml, P < 0.02) and follicle stimulating hormone (FSH) (13.2 ± 2.0 versus 10.0 ± 0.6 mIU/ml, P < 0.05), significantly 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 ± 0.13) and lower miscarriage rates (0.89 ± 0.1 versus 1.33 ± 0.24, P < 0.04). We conclude that D2 receptor alleles may be associated with reproductive success through altered gonadotrophin secretion and that this effect may be independent of ovulatory function.",
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Genetics : Association of dopamine D2 receptor gene haplotypes with anovulation and fecundity in female hispanics. / Legro, Richard; Dietz, George W.; Comings, David E.; Lobo, Rogerio A.; Kovacs, Bruce W.

In: Human Reproduction, Vol. 9, No. 7, 01.01.1994, p. 1271-1275.

Research output: Contribution to journalArticle

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T2 - Association of dopamine D2 receptor gene haplotypes with anovulation and fecundity in female hispanics

AU - Legro, Richard

AU - Dietz, George W.

AU - Comings, David E.

AU - Lobo, Rogerio A.

AU - Kovacs, Bruce W.

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N2 - Dopamine is an important neurotransmitter in the hypo-thalamic control of gonadotrophin secretion. Neuron response is mediated through one of five different dopamine receptors. We explored the association of D2 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 and exon 6 of the D2 receptor gene. A second PCR/restriction endonuclease digest was utilized to verify this. Using these assays, 185 female Hispanics (51% with known ovulatory dysfunction and 49% with normal function) were haplotyped. One allele (3) was not present in the population and there were no significant differences in remaining allele distribution between ovulatory and anovulatory patients. However, significant associations were noted between alleles and gonadotrophins and fecundity. The 4 allele had a different reproductive profile compared to the 2 allele. The 4 allele was associated with significantly higher concentrations of lutein-izing hormone (LH) (means ± SE) (19.2 ± 2.2 versus 12.3 ± 1.3 mIU/ml, P < 0.02) and follicle stimulating hormone (FSH) (13.2 ± 2.0 versus 10.0 ± 0.6 mIU/ml, P < 0.05), significantly 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 ± 0.13) and lower miscarriage rates (0.89 ± 0.1 versus 1.33 ± 0.24, P < 0.04). We conclude that D2 receptor alleles may be associated with reproductive success through altered gonadotrophin secretion and that this effect may be independent of ovulatory function.

AB - Dopamine is an important neurotransmitter in the hypo-thalamic control of gonadotrophin secretion. Neuron response is mediated through one of five different dopamine receptors. We explored the association of D2 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 and exon 6 of the D2 receptor gene. A second PCR/restriction endonuclease digest was utilized to verify this. Using these assays, 185 female Hispanics (51% with known ovulatory dysfunction and 49% with normal function) were haplotyped. One allele (3) was not present in the population and there were no significant differences in remaining allele distribution between ovulatory and anovulatory patients. However, significant associations were noted between alleles and gonadotrophins and fecundity. The 4 allele had a different reproductive profile compared to the 2 allele. The 4 allele was associated with significantly higher concentrations of lutein-izing hormone (LH) (means ± SE) (19.2 ± 2.2 versus 12.3 ± 1.3 mIU/ml, P < 0.02) and follicle stimulating hormone (FSH) (13.2 ± 2.0 versus 10.0 ± 0.6 mIU/ml, P < 0.05), significantly 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 ± 0.13) and lower miscarriage rates (0.89 ± 0.1 versus 1.33 ± 0.24, P < 0.04). We conclude that D2 receptor alleles may be associated with reproductive success through altered gonadotrophin secretion and that this effect may be independent of ovulatory function.

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